Method of obtaining derivatives of 5-substituted oxazolidine-2,4-diones in form of racemate or optic

专利摘要:
The method of producing 5-substituted oxazolidine-2,4-dion derivatives of the general formula I R Y V ° o -H-RI where R is a hydrogen atom, acetyl, C -Cj-alkylcarbamoyl, cyclohexylcarbamoyl or C -C alkoxycarbonyl; RI is a group of formula where Z is a chlorine atom or trifluoromethyl; Z is a chlorine atom, methyl, C-Cd-Alft} rmethyl; Z "a hydrogen or halogen atom, methyl or C -C-alkoxyl; Z is a hydrogen or halogen atom, methyl, and a nitro group or an alkoxy, provided that when R is a hydrogen atom, 2 is different - the photon of a hydrogen atom, and Z and Z. together are not methyl; 7 -fc a hydrogen or fluorine atom, or a nitro group; U-, hydrogen or fluorine atom; 1, C-C - alkoxy or methyl, benzyloxy group; a y, hydrogen or methoxyl, C as a paramame or optically active izscher in free form or as a pharmaceutically acceptable salt, and when R is a hydrogen atom, characterized in that the compound of general formula II 1C BUT KNy - OR 00 00 00 R, S where RJ roieeT is the indicated value; R J - C -Cj-alkyl, is reacted with phosgene in an inert organic solvent medium and the resulting compound of the general formula III O n O I and OR, R
公开号:SU1124888A3
申请号:SU813312604
申请日:1981-07-22
公开日:1984-11-15
发明作者:Каугер Шнур Родни
申请人:Пфайзер Инк (Фирма)；
IPC主号:

专利说明:

where Ry and R have the indicated values, they undergo hydrolysis to obtain the compound total 1, where R is a hydrogen atom, and if desired, separate the racemic compound of general formula I, where R is a hydrogen atom, into its optically active isomers by separating which form with an optically active amine and isolate the optically active isomer by acidification, or acylate a compound of the general formula I, where R is a hydrogen atom, the acid chloride of the corresponding acid, the corresponding anhydride or isocyanate of a compound of general formula I, wherein R J- (alkylcarbamoyl, cyclohexylcarbamoyl or C - C alkoxycarbonyl, and target pratsukt vdde isolated in racemic or optically active isomer in the free form or in pharmaceutically acceptable salt form.
The invention relates to a process for the preparation of new derivatives of 5-substituted oxazolidine-2,4-diones of the general formula ", Y ° Y ° I, where F is a hydrogen atom, acetyl, alkylcarbamoyl, cyclohexyl carbamoyl, or alkoxy carbonyl; RI is a group of the formula chlorine atom or trifluoromethyl where Z Z is chlorine atom, methyl, C-CC alkoxy, nitro or trifluoromethyl; a hydrogen or halogen atom is methyl or C; - CJ-alkoxyl; a hydrogen or halogen atom is methyl, a nitro group or an alkoxy, provided that the code R is a hydrogen atom, Zj is different from a hydrogen atom, and Zj and Z are not methyl together; Z is a hydrogen atom or fluorine, or a nitro group; at the hydrogen or fluorine atom, methyl, C ,, - C2-alkoxy or benzyloxy; YT is a hydrogen atom or methoxyl, which possess hypoglycemic activity and can be used in medicine. A known method for producing 3-pheny oxazolidin-2, 4-dione, which possesses hypoglycemic activity, consists in the fact that the malonic ester of the formula is reacted with urea in an absolute alcohol medium in the presence of sodium ethylate upon cooling 1. The purpose of the invention is to obtain new oxazolidine-2,4-dione derivatives, which can be used in medicine as substances with hypoglycemic activity. The objective is achieved by a process for the preparation of compounds of the general formula I, which consists in the fact that the compound of the general formula I BUT NH where Rj has the indicated values; Rj is C -Cj-alkyl, is reacted with phosgene in an inert organic solvent medium and the resulting compound of general formula III O W where R and R. have the indicated values are subjected to hydrolysis to give a compound of general formula I, where R is a hydrogen atom, and , divide the racemic compound of the general formula I, where R is a hydrogen atom, into its optically active isomers by separating diastereomeric salts, which are formed with an optically active amine and isolating the optically active isolager by acidification, or acylir Coziness A compound of the general formula 1, where R is a hydrogen atom, an appropriate acid chloride, the corresponding anhydride or isocyanate to form a compound of the general formula I, where R C 2 -C 2 alkylcarbamoyl5 cyclohexylcarbamoyl or C 1 -C-alkoxycarbonyl and the target product is given as a racemate or optically active isomer in free form or in the form of a pharmaceutically acceptable salt. Example 1 A.2- (2-methoxyphenyl) -2-trimethylsiloxyethanenitrile. 25 g (0.18 mol) of 2-methoxybenzaldehyde are dissolved in 150 ml of methylene chloride and cooled to. 500 mg of zinc iodide was added to the solution, after which 21.8 g (0.22 mol) of trimethylsilylcarbonitrile was added dropwise. The reaction mixture is stirred for about 65 hours at room temperature, then washed twice with saturated sodium bicarbonate solution and filtered over anhydrous sodium sulfate and the solvent is distilled off to give 2- (2-methoxyphenyl) -2-trimethylsilyloxyethanitrile as an oil (41 g, 97 %), IKS (methylene chloride): 1600, 1486, 1460, 1075 cm / e 235. B. Ethyl-1-hydroxy-1- (2-methoxyphenyl) methanecarboxyimidate (hydrochloride). 250 ml of ethanol are saturated with hydrogen chloride at 0-5 ° C and 20 g of 2- (2-methoxyphenyl) -2-trimethylsilylethanenitrile are added to the resulting solution while maintaining the temperature below 10 ° C. The reaction mixture was kept at 5 ° C for 16 hours, after which the solvent was distilled off and the residue was triturated with ether to give 1-1 hydroxy-1- (2-methoxyphenyl) methanecarboxyimidate as a hydrochloric acid salt (18.6 g, 89%, 122-124®С, with decomposition, m / e 209). C. 5- (2-Methoxyphenyl) oxazolidin2, 4-dione. 18 g (0.073 stranded) ethyl-1-hydroxy-1- (2-methoxyphenyl) methanecarboxyimidate (hydrochloride) cycneridized in 500 ml of tetrahydrofuran, cooled to 0-5 ° C, 23.6 g (0.234Moni) are added to the resulting suspension. triethylamine. Phosgene is passed through the reaction mixture with stirring for 30 minutes. Stirring at 0-5 ° C is continued for another 1 hour. Then the reaction mixture is slowly poured into 1 liter of crushed ice and the resulting product is extracted with three portions of chloroform. The chloroform extracts are combined and washed with brine, dried over anhydrous magnesium sulfate, filtered, and the solvent is distilled off to obtain a solid residue. The residue obtained is recrystallized from toluene to obtain 6.4 g of 5- (2-methoxyphenyl) -oxazolidin-2, 4-dione (42%, t, Sh1, 175177 ° C, m / e 207). The second portion (3.7 g, 24%, mp. 175-177 ° C) is recovered from the uterine toluene solution. Calculated,%: C 57.97; H 4.38; N 6.76. CioHgO N. Found,%: C 57.86; H 4.27; N 6.65. Pr and im p 2, A.2- (2-Ethoxyphenyl) -2-trimethylsiloxyethanol. According to Example 1A, 25 g (0.166 mol) .2-ethoxybenzaldehyde is converted to 2- (2-ethoxyphenyl) -2-trimethyl-1 × ethylethanol nitrile, obtained as an oil (40.6 g), X (in methylene chloride): 1594, 1481, 1073 cm-,, B. Этш1-1-hydroxy-1- (2-ethoxyphenyl) methanecarboxyimidate (hlrhydrate), According to example 1 In 40 g of 2- (2-ethoxyphenyl) -2-trimethylsh1OXiethanenitrile is converted into ethyl 1-hydroxy hydrochloride -1- (2-ethoxyphenyl) methanocarboxyimidate (31.4 g, 75%, Tn / i. 112-114 C with decomposition,). P. 5 2 Ethoxyphenyl) oxazolidin2, 4-dione. 20 g of ethyl 1-hydroxy-1- (2-ethoxyphenyl) methanecarboxyimidate hydrochloride are reacted with phosgene according to Example 1 C. To remove the product, the reaction mixture is distilled off to Dryness and distribute the resulting residue between 500 ml of water and 500 ml of chloroform. The aqueous phase is washed with two portions of fresh chloroform. The chloroform extracts are combined dried over anhydrous magnesium sulphate, filtered, the solvent is distilled off to a dry residue and recrystallized from toluene to obtain 5- (2-totoxyphenyl) oxazolidine-2,4-dione (11, 9 g, 70%, mp. 165-167 ° C m / e 221). Calculated,%: C 59.72 H 5.01; N 6.33, C ,, Found,%: C 59.79; H 5.11; N 6.35. Primer, A 2- (2-Fluorophenyl) -2-trimethylsiloxy-tannitrile. The reaction is carried out according to Example 1A, but for 16 hours. 10 g (0.081 mol) of 2-fluorobenzaldehyde are introduced into the reaction in 50 ml of methylene chloride and 9.9 g of trimethylsilylcarbonitrile (0.097 mol in the presence of zinc iodide (300 mg) J, 2- (2-fluorophenyl) -2 trimethylsiloxoethanenitrile are obtained in the form of an oil (16.1 g, 89%, m / e 223), X (in methylene chloride): 1709, 1621, 1600, 1176, B. Ethyl-1- (2-Fluorophenyl) -1-hydrochloro-methancarboxyimidate (hydrochloride) According to Example 1 In 16 g of 2- (2-fluorophenyl) -2-trimethylsiloxyethanethi-nitrile in 400 ml of an ethanolic solution of hydrogen chloride is converted into ethyl chlorohydrate 1- (2- fluorophenyl) -1-hydroxymethane carboxyimidate (14.9 g, 89%, 129-13lc with decomposition). Calculated,%; C 51.40; H 5.61j N 6.00. C oH jO NF-HCl Found:% C 51.22; H 5.27; N6.16., C.5- (2-Fluorophenyl) oxazolidine 2, 4-dione. According to Example 1 C, the reaction time is 2 hours at room temperature stages of transfer of phosgene, 14.5 g (0.062 mol) of ethyl- (2-fluorophenyl) -1-hydroxymethanecarboxyimidate hydrochloride in 500 ml of tetra-hydrofuran are transformed into recrystallized from tapuol 5- (2-fluorophenyl) oxazolidine-2,4- Dione (7.32 g, 60%, so pl. 129-131 C). Calculated,%: C 55.38; H 3.10; N 7j18. CgHgOjNF. Found,%: C 55.25; H 3.23; N 7.15. Example 4, A.2- (5-Chloro-2-methoxyphenyl) -2-trimethylsiloxyethanenitrile. According to Example 3 C, b g (35 mol) of 5-chloro-2-methoxybenzaldehyde is reacted with 4.16 g (42 mol) of trimethylsilylcarbonitrile in the presence of 200 mg of zinc chloride. The reaction mixture is diluted with 50 ml of methylene chloride, followed immediately by the separation of 2- (5-chloro-2methoxyphene1) -2-trimethylsiloxyethanenitrile as an oil (9.1 g, 97%, m / e 271/269), IR (in methylene chloride): 16P, U93, 1105 cm B. Ethyl 1- (5-chloro-2-methoxy) -1hydroxymethanecarboxyimidate. Method A „According to Example 1, 9 g of 2- (5-chloro-2-methoxyphenyl) -2-trimethylsiloxyethanenitrile in 250 ml of a valuable ethanolic solution of hydrogen chloride is converted to eth1-1- (5-chloro-2-methoxy1-hydroxymethanecarboxyimidate hydrochloride as a solid substances). The hydrochloride is converted to the free base by distribution between methylene chloride and saturated sodium bicarbonate solution. The extract in methylene chloride is washed twice with additional portions of sodium bicarbonate and brine, and distilled over anhydrous magnesium sulfate, filtered and the solvent is distilled to dryness to obtain the free base as a viscous oil (5.2 g, 70%, m / e 245/243 ), X (KBG): 1672, 1493 cm. Method B. 100 ml of ethanol are cooled in a bath of ice water and hydrogen chloride is passed through it for 1 min. Out of 4 g of 2- (5-chloro-2methoxy) -2-trimethylsiloxyethanenitrile, a suspension is prepared in the cold in an ethanolic solution of hydrogen chloride. To solubilize the nitrile, 50 ml of carbon tetrachloride are added to the mixture and the cooled mixture is stirred for 2 minutes, then concentrated to dryness to give 5-chloro-2-methoxybenzaldhydrogen (2.58 g), m.p. 71-74 C, m / e 199/197. After recrystallization from a mixture of chloroform and hexano, purified cyanohydrin is obtained (mp. 72-74 ° C), 200 mg of 5-chloro-2-methoxybenzaldehyde cyanohydrin are placed in 10 ml of a saturated ethanolic solution of hydrogen chloride at 0-5 ° C and the solution is kept for 4 h at 0 ° C. The solvent is then distilled off from the reaction mixture to obtain a crude product. After recrystallization from ethanol / ether, purified ethyl 1- (5-chloro-2-methoxyphenyl) -1-hydroxymethinecarboxyimide HG is obtained as a hydrochloric acid salt (256 mg, 91%, mp. 142-144 ° C with decomposition, m (e - 245/243), p. 2 (5-HoUr-2-methoxyphenyl) oxazolidin-2 4-dione. Method A. According to Example 3 C, but using 2 eq, triethylamine and extracting the product with methylene chloride, followed by cooling with ice, 5.5 g (0.023 mol) of ethyl 1 - (5-chloro-2 - methoxyphenyl) -1 hydroxymethanecarboxyimidate in 250 ml of tetrahydrofuran is converted to 2- (5 chloro-2-methoxyphenyl) oxazolidine-2,4-dione in recrystallized from toluene (3.81 g, 69%, ° T. mp, 178-180 ° C, m / e 243/241), C, 49.70; H 3.34; Calculated 5.80. C ,, JlgO, NCI. Found: C 50.05; H 3.46; 5.82. Method B. 14.2 g (0.05 mol) of ethyl 1- (5-chloro-2 methoxyphenyl) -1-hydroxymethane-carboxy-imidate (as a hydrochloric acid salt) are suspended in 350 ml of tetrahydrofuran and cooled in an ice-bath. To the solution was added 16.2 g (0.16 mol) of triethylamine, after which the reaction mixture was cooled and phosgene was passed through it for 2 hours; during this period, according to thin layer chromatography (ethyl acetate-chloroform 1: 1 mixture), only the intermediate product 5- (5-chloro-2-methoxyphenyl) 4 ethoxy-2-oxazolone is isolated, which is isolated by distilling off the solvent dry and distribute the residue between ethyl acetate and water. The extract with ethyl acetate is washed with a saturated three-bicarbonate solution, dried over anhydrous magnesium sulfate, and from 1 to 8, the solvent is distilled to give an intermediate product (m / e 271/269). The reaction mixture is allowed to warm to room temperature, after which the passage of phosgene is continued for another 1 hour and the reaction mixture is stirred at room temperature for 16 hours. Then the reaction of the mixture is slowly poured into 1 liter of crushed ice and extracted three times with 250 ml portions of chloride methylene. The extracts are combined, washed with brine, dried over anhydrous magnesium sulphate, filtered and the solvent is distilled off to dryness, yielding 14.7 g of product. The recrystallization is carried out in various ways from mixtures of ethyl acetate with toluene and acetic acid with hexane. The total amount of the product (14.2 g) is extracted with a mixture of 80 ml of water and 64 ml of 1N solution of OKifsi sodium hydrate, extracted with toluene (one portion of 140 ml and 2 portions of 50 ml), treated with activated carbon, filtered and precipitated, pouring into 100 ml ZN hydrochloric acid solution with faster stirring. 10.4 g of purified 5- (5 chloro-2-methoxyphenyl) -oxazole din2, 4-dione are obtained (86%, mp. 178.5-180,) and Example 5. A.2- (5 -Fluoro-2-methox1 enyl) -2trimethylsiloxy-tetanenitrile. According to Example 1 A, excluding that the reaction time is 4 days at room temperature, 9.5 g (0.062 mol) of 5-fluoro-2-methoxybenealdehyde in 50 ml of methylene chloride are reacted with 7.3 g (0 , 07.4 mol) of trimethylsilylcarbonitrile in the presence of catalytic amounts of zinc iodis to give 2- (5-fluoro2-methoxyfensh1) -2-trimethylsiloxy-ethanethanine (12.5 g, yield 79%, oil, m / e 253), ICS (in methylene chloride): 1504, 1200 cm. B. Ethyl 1- (5-fluoro-2methoxyphenyl) -1-hydroxymethanecarboxy syimidate hydrochloride. According to example 1B, except that the reaction is 2 hours at 12.4 g of 2- (5-fluoro-2-methoxyphenyl) -2-trimethylsiloxyethanethnenrnl in 300 ml of an ethanolic solution of hydrogen chloride, is converted into eth1-1- (5-fluoro -2-labels-siphenyl) -1-hydroxymethanecarboxyimndate (9.9 g, yield 77%, mp. 135137 0 with decomposition). 91 Calculated,%: C 50.10; H 5.73; N 5.31. .HCt Found:% C 49.88; H.5,73; N 5.55. C. 5- (5-fluoro-2-methoxyphenyl) oxazolidin-2, 4-dione. According to Example 3 of C, 9.9 g of ethyl 1- (5-fluoro 2-methoxyphenyl) -1-hydroxymethanecarboxyimidate hydrochloride in 500 ml of tetrahydrofuran are recrystallized from toluene 5- (5-fluoro-2-methoxyphenyl) oxazolidin-2, 4-dione (5.12 g, yield 60%, mp 186-188 C, m / e 225). Calculated,%: C 53.34; H 3.58; N 6.22. C. Found,%: C 53.33; H 3.63; N 6.12, Example 6. A. 2- {2-chlorophenyl) -2-trimethylsiloxyethanenitrile. 15 g (0.107 mol) of 2-chlorobenzaldehyde is cooled in an ice bath and 500 mg of zinc iodide are added with stirring, and then 12.7 g (0.128 mol) of trimethylsilylcarbonitrile are added dropwise. The reaction mixture is stirred for 16 at room temperature, diluted with methylene chloride, washed with three portions of saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated to give 2- (2-chlorophenyl) 2-trImethylsiloxyethanethi-nitrile as an oil ( 24.1 g, yield 94%), IR (in methylene chloride): 1587, 1464, 1045 cm V. ethyl-1-chlorophenyl chlorohydrate | 1-hydroxymethanecarboxyimidate. According to Example 1, 15 g of 2- (2-chlorophenyl) -2-trimethylsiloxyethanenitrile in 375 ml of a saturated ethanolic solution of hydrogen chloride is converted into ethyl chlorohydrate-1- (2-chlorophenyl) -1-hydroxymethanedcapoximemide (13.4 g, yield 85%, mp. 127129 C with decomposition), IR (KVg): 3125, 3003, 2899, 1653, 1531 cm C.5- (2-Chlorophenyl) oxazolidine-2,4dione. Ethyl 1- (2-glorphenyl) -1-hydroxymethanecarboxyimidate hydrochloride (13 g, 52 mmol) is shifted from 350 ml of tetrahydrofuran and the mixture is cooled in an ice-water bath, B 16.77 g (0.166 mol) are added. triethylamine and passed through the reaction mixture while first stirring for 45 minutes at phosgene. After keeping for another hour at the same temperature, the reaction mixture was slowly poured into 1 l of crushed ice, and after separation and recrystallization from toluene according to Example 3, 5- (2-chlorophenyl) oxazolidin-2,4-dione (7.43 g , yield 687., mp,), Calculated,%: C 51.08; H 2.68; N 6.62; Found: C 50.73; H 2.93; N 6,6i; Example 7, A, 2- (3-Chlorfensch1) -2-trimethylsiloxyethanenitrile. According to Example 6A, 25 g (0.178 mol) of 3-chlorobenzaldehyde was reacted with 21.2 (0.2t4 mol) of trimethylsilylcarbonitrile in the presence of zinc iodide (500 mg) to give 2- (3-chlorophenyl) -2-trimethylsiloxyethanenitrile as an oil (39.2 g, yield 92%), IR (in methylene chloride): 1952, 1570, 1468, 1183 cm B, ethyl 1- (3-chlorophenyl) -2-hydroxymethanboxoxymidate hydrochloride. According to Example 1 B.10 g of 2- (3-chlorophenyl) -2-trimethylsiloxyethanenitrile in 250 ml of a saturated ethanolic solution of hydrogen chloride is converted into ethyl- (3-chlorophenyl) -2-hydroxymethancarboximidate hydrochloride (9.1 g, yield 87%, t , pl, 117-120c with decomposition), IR (KVg): 3106, 2817, 1773, 1639 cmL C, 5- (3-Chlorfensh1) oxazolin-2,4dione. According to Example 1, C 9 g (38 mmol) of ethyl 1- (3 chlorophenyl) -1-hydroxymethanecarboximidate hydrochloride in 250 ml of tetrahydrofuran is converted into toluene 5- (3-chlorophenyl) oxazolidine 2, 4-dione (4.5 g, yield 56%, mp. 142144 C). Calculated,%: C, 51.08; H 2.86; N 6.62, CgHgOjNCI Found,%: C 51.24; H 2.98; N 6.76, Example 8, A, 2- (2-Methoxy-5-nitrophenyl) -2-trimethylsiloxyethanenitrile, 3.4 g (0.019 mol) of 2-methoxy-5-nitrobenzaldehyde are dissolved in 125 ml of chloride methylene; Zinc iodide (50 mg) and trimethylsilylcarbonitrile are added to the mixture successively.
after which the reaction mixture is stirred for 2 hours at room temperature. The mixture is then washed with two portions of saturated sodium bicarbonate solution and one portion of brine, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness, to give 2 (2-methoxy-5-nitrophensh1) -2-trimethylsiloxyethanethi-nitrile (5.0 g, 94%, mp. 108-111 ° C, m / e 280), IR (KVg): 1610, 1592, 1511, 1342, 1269 cm
B. Ethyl-1-HYDROXY-1 hydrochloride (2-methoxy-5-yitrofensh1) methancarb-xnm date. According to Example 1B, but when the reaction is carried out for 1 hour at 5 g of 2- (2-methoxy-5-nitrophenyl) -2-trimetp, ls11Loxy) ethanenitrile in 150 ml of a saturated ethanolic solution of hydrogen chloride, it is converted HYDROXY1- (2-methoxy-5-nitrophenyl) methanecarboxyimidate (4.64 g, yield 89%, mp 158-161 ° C with decomposition,
m / e 254), IR (KVg): 3077, 2841, 1639, 1592, 1515, 1313 cm.
C.5- (2-Methoxy-5-nitrofenён1) oxazolidin-2, 4-dione. According to Example 1 C, 4.5 g (0.015 mol) of ethyl 1-hydroxy-1- (2-methoxy-5-nitrophenyl) methanecarboxyimidate hydrochloride: 400 ml of tetrahydrofuran are converted
into the crude target product. After recrystallization from ethanol, purified 5- (2-methoxy-5-nitrophenyl) -oxazolidin-2,4-dione is obtained (2.3 g, 60% yield, mp 205-20 ° C)
Calculated,%: C 47.62; H 3.20; N11.11.
C-, eObNa
Found,%: C 47.51; H 3.19; N 11.06.
PRI me R 9.
A. 2- (3-Fluorophenyl) -2-trimethylsilox-ethanenitrile. 10 g (0.081 mol) of 3-fluorobenzaldehyde is dissolved in 50 ml of ether and cooled in a bath containing a mixture of ice-water. 300 mg of zinc iodide are added to it, after which 9.6 g (0.097 mol) of trimethylsilylcarbonitrile are added dropwise. The reaction mixture is stirred for 16 hours at room temperature, 200 ml of ether are added, washed with three portions of sodium bicarbonate and one portion of brine, and dried over anhydrous magnesium sulfate.
 filtered and concentrated to give 2- (3-fluorophenyl) -2-trimethylsilox-1 ethanenitrile as an oil (16.8 g, yield 93%, m / e 223), X (methylene chloride): 1626, 1600, 1493, 1067
B. Ethyl-1- (3-fluorophenyl) -1-hydroxymethanecarboximium hydrochloride According to Example 1 In 16.6 g of 2- (3fluorophenyl) -2-trimethyl-1-ethane ethanenitrile in 400 ml of a high-grade ethanolic solution of hydrogen chloride is converted into ETSH1-1- (hydrochloride) -fluorophenyl) -1-hydroxymethanecarboximidate (16.4 g, yield 95%, mp. 121-123C
with decomposition, m / e "197).
C.5- (3-Fluorofensch1) oxazolidin2, 4-dione. According to Example 1, with the exception that the reaction time is 16 hours at room temperature after passing phosgene in the cold and that the product is extracted with chlorine methylene after quenching it in crushed ice, 16 g (0.068 mol) of ethyl-1 - ( -fluorophenyl) -1 -hydrox eta carboxyimidate is converted into 5- (3-fluoro} fensh1) oxazolidin-2,4-dione recrystallized from toluene (7.51 g, yield 56%, mp. 147-149 ° C) .
Calculated,%: C 55.38; H 3.10; N 7.18.
CgH ..
Found,%: C 55.21; H 3.17; N 7.31.
Example 107
 And 2-CH2-Metsh1phenyl) -2-trimethylsiloxyethanethanol. According to Example 6A, except that the reaction time was 5 days at a temperature (m at a temperature of 15 g (0.125 mol) of 2-methylbenaldehyde) and 1479 were reacted. -C2-metsch1phenyl) -2-trimethylsiloxyethanenitrile in the form of oil (25.6 g, yield 93%, m / e 219), X (methylene chloride): 1600, 1484, 1450, 1124.
AT.  Ethyp-1-hydroxy-1 (2-metsh1phenyl) methanecarboxyvdate hydrochloride, According to the example t In 15 g of 2- (2-mbT1itsphenyl) -2-trimetylsiloxyethylenth | rshga in 350 ml of a saturated ethanolic solution of hydrogen chloride is converted into an ethyl ethyl chloride-1-GKDRO-1-GKDRO-ethyl-1-GKDRO-1-GKDROE-1-GKDRO-ethyl-1-GKDROE-1-GKDRO-ethyl-1-GKDROHETHEPH; -1 (2-methylphenyl) methanecarboxychdate (14.4 g, yield 92%, t. square  123-125 С with decomposition, m / e "193).  13 Calculated,%: C 57.51; H 7.02; N 6.10.  , jO N-HCi Found,%: C 57.35; N. 6.75; N 6.16.  WITH.  5- (2-Methylphenyl) 6xazolidin2, 4-dione.  According to Example 1 C14, A is ethyl 1-hydroxy-1- (2 methylphenyl) methancarboxy. imidate in 500 ml of tetrahydrofuran is converted into 5- (2-methylphenyl) -oxazolidin-2,4-dione recrystallized from toluene (9, 1 g, yield 77%, t, pl.  111113 ° C, m / e 191).  Calculated,%: C, 62.82; H 4.74; N 7.33.  C HgOjN Found,%: C 62.56; H 4.62; N 7.30.  Example 11  BUT.  2- (2-Trifluoromethylphenyl) -2-trimethylsiloxyethanethanol.  According to Example 6A, 10 g (0.057 mol) of 2-trI fluoromethylbenzaldehyde was reacted with 6.73 g (0.068 mol) of trimethylsilylcarbonitrile in the presence of 250 mg of zinc iodide to give 2- (2-trifluoromethylphenyl) trimethylsilyoxyethanitrile in the form of ma la (15.1 g, yield 97%), IR (methylene chloride):; 1 31 6, 1170, 11:24.  B, Ethyl-1-hydroxy-1- (2-trifluoromethylphenyl) methanecarboximidate.  According to Example 1B and 4B (Method A), 15 g of 2- (2-trifluoromethylphenyl) -2-trimethylsiloxyethanenitrile in 450 ml of a saturated ethanolic solution of hydrogen chloride are converted to ethyl1-HYDROXY-1- (2-trifluoromethylphenyl) methancarboxyimidate (10, 2 g, yield 75%), IR (KBG): 1661, 1385, 1312 C.  According to Example 4 C (method 10 g of ethyl 1-hydroxy-1- (2-trifluoromethylphenyl) methancarboxyimidate in 500 ml of tetrahydrofuran is converted into 5- (2-trifluoromethylphenyl) oxazolidine 2, recrystallized from toluene), 4-dione (5.3 g, yield 54%, t. square  9, m / e 245).  Calculated,%: C, 48.99; H 2.47; N 5.71 C. oH. OjNFj Found,%: C 48.68; H 2.57; N 5.60.  Example 12  BUT.  2- (3-phenoxyphenyl) -2-trimethyl siloxyethane nitrile.  According to Example 6A 1, 5 g (0.076 mol) of 3-phenoxybenzaldehyde is reacted with tr 8 methylsilylcarbonitrile (9.01 g, 0.091 mol) in the presence of 500 kg of zinc iodide, resulting in 2- (3-phenoxyflenyl) -2 -trimethylsiloxyethanenitrile in the form of an oil (21.8 g, yield 96%, m / e 297), IR (KBr): 1587, 1481,.  1140 cm  B. Ethyl 1-hydroxy-1 (3-phenoxyphenyl) methanecarboxyimidate hydrochloride.  According to Example 1, 15 g of 2- (3-phen-, oxyphenyl) -2-trimethylsiloxyethanenitrile in 350 ml of a saturated ethanolic solution of hydrogen chloride is converted into chloro-1 "ethyl de-1-hydroxy-1- (3-phenoxyphenyl) methanecarboxyimidate (13.5 g , yield 88%, t. square  120123 С with decomposition, m / e 271).  C. 5- (3-phenoxyphenyl) oxazolidin2, 4-dione.  According to Example 1 C, 13 g of ethyl 1-hydroxy-1- (3phenoxyphenyl) methancarboxyimidate hydrochloride in 500 ml of tetrahydrofuran are converted and recrystallized from toluene 5- (3-phenoxyphenyl) -oxazolidin-2,4-dione (7.5 g, yield 66% , t square  104Yub S, m / e 269).  Calculated Z: C 66.9t; H 4.12; N 5. 20.  b5 ii04N Found,%: C 66.88; H 4.14; N 5.21.  Example 13  BUT.  2- (2-Benzyloxyphenyl) -2-trimethylsiloxyethanethanol.  According to Example 1A, 25 g (0.118 mol) of 2-benzyloxybenzaldehyde in 250 ml of methylene chloride are reacted with 14.06 g (0.142 mol) of trimethylsilylcarbonyl in the presence of zinc iodide (500 mg), to give 2- (2-benzene-1-oxyphenyl) ) -2-trimethylsiloxyethanethanol: silt in the form of oil (35.6 g,), X (methylene chloride): 1605, 1493, 1418, 1220.  B. Ethyl 1- (2-benzyloxyphenyl) -1hydroxymethanecarboxyimidate.  According to example 1B and 4B (method A), 20 g of 2- (2-benzyloxyphenyl) -2-trimethylsiloxyethanenitrile in 500 ml of a saturated ethanolic solution of hydrogen chloride are converted into ethyl 1- (2benzyloxyphenyl) -1-hydroxymethancarboximidate as a viscous oil (13.2 g, 72% yield), IR (methylene chloride): 1661, 1605, 1493, 1379 cm-.  C. 5- (2-Benzipoxyphenyl) oxazolidin-2, 4-dione, According to example 4 of C 15 (method A), 13 g of ethyl 1- (2-benzyloxy phenyl) -1-hydroxymethanecarboxyimidate in 350 ml of tetrahydrofuran are converted into recrystallized from toluene 5 - (2-benzyloxyphensh1) -oxazolidine 2,4-dione (7.23 g, yield 55%, t ,. 1sh.  191-193C, m / e 283).  Calculated,%: C, 67.84; H N 4.94.   C1, H, z04 “Found%: C 67.84; H 4.67; N 4.96.  Example 14  A. 2- (3-Trifluoromethylphenyl) -2-trimethylsiloxye tannitrile.  With reference to Example 6 A, 10 g (0.057 mol 3-three fluoromethylbenzaldehyde is reacted with 6.78 g (0.068 mol) of trimethyl silylcarbonitrile in the presence of zinc iodide (250 mg) to give 2- (trifluoromethylphenyl) -2-trimethylsiloxyethanethanitrile in the form of oil (15.6 g), X (methylene chloride): 1342, 1170, 1136 cm B. Ethyl 1-hydroxy-1- (3-trifluoromethylphenyl) methanecarboxyimidate.  According to example 1B and 4B (method A), 15.5 g of 2- (2-trifluoromethylphenyl) -2trimethylsiloxyethanenitrile in 500 ml of a saturated ethanolic solution of hydrogen chloride are converted into ethyl 1-hydroxy-1- (3-trifluoromethylfennl) methanecarboxyimidate (9 , 6 g, yield 70%), IR (KBG): 166 1389, 1333, 1305, D1163, 1117 C. 5- (3-Trifluoromethylphenyl) oxazolidin-2,4-dione.  9.5 g (0.038 mol of ethyl-t-hydroxy-1- (3-trifluoromethylphenyl) methancarboxyimidate) are dissolved in 500 ml of tetrahydrofuran and cooled to.  0-5 ° C.  7.68 g (0.076 mol) of triethylamine is added to the solution and passed through it for 35 minutes at phosgene.  After stirring for 1.5 hours, partitioning and recrystallization according to Example 1 C, 5- (3-trifluoromethylphensh1) oxazolidin-2,4-dione (6.4 g) 9% is obtained, T. Ш1.  93-96 ° C).  After the second recrystallization from toluene, a purified product is obtained (4.9 g, yield (total) 53%, t. square  97-99 C, m / e-245).  calculated,% C 48.99; H 2.47; N 5.7V C oH OjNFs C 48.93; H 2.64; Found,%: N 5.63.  15.  Example 8 AO 2- (5-Chloro-2-methoxy-3 m-methylphenyl) -2-trimethylsiloxyethanenitrile "According to Example 1A 1.98 g, (10.7 mmol) 5-chloro-2-methoxy-37" ethylben3aldehyde in 50 ml of methylene chloride is introduced into reactio with trimethylsilylcarbonitrile (g, 12.8 mmol) in the presence of IODISTOROZZK (50 mg), to give 2- (5-chloro-2-methoxy-3-m-tfaylfile) -2trimethylsiloxyethanethylnitrile as an oil (3 , 0 g, yield 99%, m / e 285/283;), IR (methylene chloride): 1471, 1117 1096 cm - B. Ethyl-1- (5-chloro-2methoxy-3-methylphenyl) -t-hydroxnmethanarboximidate chloro-indigrate.  100 ml of ethanol are saturated with hydrochloric acid at the solution. T- 2- (5-chloro-2-methoxy-3-methylphene) -2trimethylsiloxyethynitrile in S ml of ethanol is added dropwise to K solution, and the temperature of the reaction mixture is kept below 1 (C "Then the reaction mixture permeates with.  For about 1 hour, the solvent is taken to dryness and the residue is triturated with ether to obtain ethyl 1- (5-chloro-2-methoxy-3-methyl-1-hydroxymethyl) -1-hydroxydroxymethanecarboxyimidate hydrochloride (2.67 g, yield 89%, t. square  131-133 С with decomposition, IR (KVg): 1653, 1538, 1488, 1227, 1093 cm.  C. 5- (5-Chloro-2-methoxy-3-methylphenyl) oxazolidin-2,4-dione.  According to Example 3 C, except that instead of chloroform, for extraction of the product following the haschevium, methylene chloride is used, 2.5 g (8.5 mmol) of these 1- (5-chloro-2-methoxy 3-meth-1-phenyl) - 1 Hydrximethanecarboxyimidate in 250 ml of tetrahydrofuran is reacted with phosgene in the presence of triethylamine (2.7 g, 27 mmol).  The propellant is dispensed by slowly pouring the reaction mixture into 1 liter of crushed ice.  The aqueous phase is separated and extracted with three portions of methylene chloride.  The organic phase and extracts are combined and the solvent is distilled off from the combined solution until dry.  The crude product is extracted with a 1N sodium hydroxide solution, extracted with ether, acidified with 3N hydrochloric acid, and the resulting product precipitated (1.81 g, yield 83% t. square  184-186 C).  After recrystallization from toluene, 5- (5-chloro-2-methoxy-3-methylphenyl oxazolidine-2,4-dione) ophthalmic 171 (1.57 g, total yield 72%, t.) Are obtained. square  187-189 ° C).  Calculated,%: C, 51.67; H 3.94; N. 5.48 C ,, H ,, 0, NC1 Found,%: C 51.37; H 3.97; N 5.66.  Example 16  A. 2- (2-Chloro-6-methoxyphenyl) -2trimethylsiloxyethanenitrile.  According to Example 9A, except that the reaction is carried out for 1 hour at room temperature, 3.6 g (0.021 mol of 2-chloro-6-methoxybenzaldehyde in 100 ml of ether is reacted with 4.30 g (0.042 mol) of trimethylsilylcarbonitrile in in the presence of zinc iodistog (100 mg), resulting in 2- (2-chloro-6-methoxyphenyl) -2-trimethylsiloxyethanenitrile as an oil (5.62 g, 99% yield).  NMR (CDClI), eA indicates the presence of a trimethylsilyl peak at 0.3 m. d. , peak С-Н product at about 6.7 m. d. , lack of aldehyde peak С-Н in the region of 10.4 m. d.  B. Ethyl 1- (2-chloro-6methoxyphenyl) -1-hydroxymethanecarbok imidate hydrochloride.  According to Example 1B, except that the reaction mixture was kept for only 1 hour at 0-8 ° C, 5.52 g (0.021 mol) of 2- (2-chloro-6-methoxy-phenyl) -2-trimethylsiloxyethanenitrile in 200 ml of saturated ethanol hydrogen chloride solution was converted into ethyl 1- (2 chloro-6-methoxyphenyl) -1-hydroxymethyl hydroxyimidate hydrochloride, which had the appearance of a hygroscopic solid (5.55 yield 95%, t. square  131 ° C with decomposition).  Calculated,%: C 47.16; H 5.40; N 5.00.  C. H CjNOj Found,%: C, 47.05; H 5.35; N 4.72.  C. 5- (2-Chloro-6-methoxy) oxazoline 2,4-dione.  According to Example 3A, ethyl 1- (2-chloro-6-methoxyphenyl) -1-hydroxymethanecarboxyimidate 50 chlorine hydrate in 250 ml of tetrahydrofuran is converted into 4: 1 5- (2-chloro-6-methoxy) recrystallized from a mixture of toluene and hexane. ) oxazolin-2,4-dione (3.42 g, yield 74%, tons square  197-200 ° C).  For further purification of the product, recrystallization from acetone with replacement by ethyl acetate according to Example 92 is used.  8 Example 17.  A. 2- (2-Chloro-6-fluorophenyl) -2-trimethylyloxyethanenitrile. According to Example 9A, except that the reaction was carried out for 2.5 hours at room temperature, 10 g (0.063 mol) of 2-chloro-6-fluorobenzaldehyde in 150 ml of ether was reacted with 12.5 g (16 ml, 0.126 mol) of trimethylsilylcarbonitrile in the presence of 100 mg of zinc iodide, resulting in 2- (2-chloro-6-fluorophenyl) -2-trimethyl-siloxyethanenitrile in the form of an oil (18.2 g of product from which the solvent is not completely removed), NMR cAj indicates the presence of a C-H peak at 5.55 m. d.  (split by fluorine) and the absence of aldehyde C-H (in the region of about 10.4 m. d. ).  B. Ethyl 1- (2-chloro-6fluorophenyl) -1-hydroxymethanecarboxyimidate hydrochloride.  According to example 1B, except that the reaction is carried out for 40 minutes at 0-5 ° C, obtained in the previous example, 2- (2-chloro-6-fluorophenyl) -2-trimethylsiloxyethanethanenitrile, from which the solvent was not completely removed (16.2 g ), is introduced into the reaction in 540 ml of an exemplary ethanolic solution of hydrogen chloride, resulting in ethyl chlorohydrate 2 (2-chloro-6-fluorophenyl) -1-hydroxymethanecarboxyimidate (15.2 g, t. square  129130 ° C), ЖР (C, jHgOH), f-, shows the presence of a SI peak at 6.1 m. d. shifted to 5.5 m. d.  in the original product.  C. 5- (2-Chloro-6-fluorophenyl) oxazolidin-2, 4-dione.  15.0 g (0.056 mol) of ethyl 1- (2-chloro-6-fluorophenyl) -1-hydroxymethanecarboximidate hydrochloride and 16.8 g (23.3 ml, 0.167 mol) of triethylamine are dissolved in 560 ml of tetrahydrofuran and cooled to .  Phosgene is passed through the reaction mixture for 35 minutes.  The reaction mixture is then stirred for 2.5 hours at room temperature, drunk in 600 ml of crushed ice, and extracted with three portions of ethyl acetate.  The extracts are combined, washed with water, brine, dried over anhydrous magnesium sulphate, filtered and the solvent is distilled off in vacuo.  receiving 14.4 g of product.  After recrystallization from toluene, purified 5- (2-chloro-6-fluoro (benyl) oxyazolidin-2, 4-dione (10.7 i-, yield 83%, m. square  ISS-ISS C), IR (KBr): 1820, 1740 cm. Calculated:% С 47.08; H 2.20 ;, N 6.09 C HjOiNFCl Found:% C, 29.29; H 2.43; No. 6.14.  PRI me R 18, A.  2- (5-Bromo-2-methoxyphenyl) -2trimethylsiloxyethanethanol.  15 g (0.069 mol) of 5-bromo-2-methoxybenzaldehyde in 100 ml of methyl chloride are introduced into the reaction with 8.2 g (10.5 ml, 0.083 mol) of trimethylbenzylcarbonitrile in the presence of 100 mg of zinc iodide according to Example 1.  After keeping the reaction mixture for 24 hours at room temperature, it was diluted with 100 ml of methylene chloride and the product obtained was prepared according to Example 1, to give 2- (5-bromo-2-methoxyphenyl) -2-trimethylsilone seatanenitrile (21.1 g , solid product Rf (ethyl acetate: chlorophop a 1: 1) 0.78, NM (CDCl,), / -, M. D. : 0.3 (9H); 4.0 (ZN) 5.7 (1H); 6.7-7; 8 (ЗН).  B. Ethyl-1- (5-bromo-2methoxyphenyl) -1-hydroxymethanecarbroxyimidate hydrochloride. According to Method 5B, 20 g of 2- (5-bromo-2-methoxyphenyl) -2-trimethyloxyethanenitrile in 500 ml of a saturated ethanolic solution of hydrogen chloride are converted into chlorine-1- (3-bromo-2-methoxyphenyl) -1-hydroxymethanecarboxyimidate hydrochloride (17.4 g, solid), NMR (1: 1 CDCljtflMCO), cL, m d. : 1.5 (ЗН); 4.0 (3N); 4.6 (2H); 5.8 (1H); 6.97, 9. (G)  C. 5- (5-Bromo-2-methoxyphenyl) oxazolidin-2, 4-dione.  According to Example 1, C, 16.6 g (0.049 mol) of 2- (5-bromo 2-methoxyphenyl) -2-trimeish1Syloxyethanenitrile in 320 ml of tetrahydrofuran is reacted with phosgene.  After stirring the reaction mixture for 16 hours at room temperature, it is quenched in 1 liter of crushed ice and extracted with two portions of 500 ml of ethyl acetate.  The extracts in ethyl acetate are combined and washed with two 200 ml portions of brine-, dried over anhydrous magnesium sulfate, filtered, and the solvent is distilled off to obtain a solid residue.  The residue is recrystallized from toluene.  resulting in a purified 5- (5-brom-2-methoxyphenyl) oxazodidine-2,4-dione (10.7 g, t. square  166-167 0).  Calculated,%: C, 41.48; H 2, 82; N 4.84.   Found,%: C 41.94; H 2.82; N 4.93.  Example 19  A. 2- (5-Chloro-2-ethoxyphenyl) -2-trimethylsiloxy-tannitrile.  According to Example 1A, 10 g (0.054 mol) of 5-hpI2-ethoxybenzaldehyde c. 100 ml of methylene chloride are reacted with 6.4 g (8.2 ml, 0.065 mol) of tri-, methylsilylcarbonitrile in the presence of 100 mg of zinc iodide.  After 2.5 extensions of the mixture at room temperature, the product was dispersed according to Example 52, to give 2- (5-chloro-2-ethoxy-1) -2-trimethylsiloxyethanenitrile in the form of an oil which crystallizes on standing (14.8 g), NMR ( CH, C1: CHC1d), e, m. d. : 0.3 (9H); 1.5 (3N); 4.2 (2H) {5.8 (1H); 6.7-7.6 (ЗН).  B. Ethyl 1- (5-chloro 2-ethoxyphenyl) -1-hydroxymethanecarboxyimidate.  According to example 1B, but when carrying out the reaction for 2 hours at 14 g of 2- (5-chloro-2-ethoxyphenyl) -2trimethylsiloxyethanine, in 350 ml of a saturated ethanolic solution. . .  hydrogen chloride is converted to the product hydrochloride.  The operations of Example 11 are then carried out, but using chloroform instead of methylene chloride, and the hydrochloride is converted into the free base to ethyl 1- (5-chloro-2-ethoxyfennp) -1-hydroxymethanecarboxyimidate (8.76 g, a soft solid ), NMR (COC1), (L: 1.1-1.6 (two, triplet, 6H); 3, (two quartets, 4H); 5.5 (singlet, 1H); 6.9-7j3 (multiplet , ZN).  C. 5- (5-Chloro-2-ethoxyphenyl) oxazolidin-2, 4-dione.  According to Example 18 C, but with the use of 2.3 eq of triztilamine, 8.0 g (0.029 mol) of ethyl 1- (5-chloro-2-toxifen1) -1 hydroxymethanecarboxylic acid in 300 ml of tetrahydrofuran is reacted with phosgene.  After stirring the reaction mixture for 2 hours or more at room temperature, the gel is dispersed according to. Example 54, while replacing ethyl acetate with chloroform, resulting in 5- (5-chloro-2-ethoxy-phenyl) -xazolidin-2,4-dione (2.7 g, t.) recrystallized from toluene. square  197-199 C).  Calculated,%: C, 51.68; H 3.94; N 5. 48.  C, Found,%: C 51.59; H 3.99; N 5.44.  Example 20  A. 2t- (2-Ethoxy-5-fluorophenyl) -2-trimethylsilylethanenitrip.  According to Example 19A, 10.2 g (0.06 mol) of 2-ethoxy-5-fluorobenzaldehyde in 120 ml of methylene chloride are reacted with 12 g (15.3 ml, 0.12 mol) of trimethylsilylcarbonitrile in the presence of zinc iodide. (150 mg), resulting in 2- (2-ethoxy-5-fluoro-phenyl) -2-trimethylsyl1-ethanenitrile as an oil (14, G g, yield 88%), 5IMP (CDClj), / -: 0.3 ( singlet, 9H); 1.5 (triplet, ZN); 4.1 (quartet, 2H); 5.8 (singlet,. 1H); 6.8-7.6 (multiplet, 4H).  B. Ethyl-1 (2-ethoxy-5 fluorophenl) -1-hydroxymethyl carboxyimidate hydrochloride.  According to Example 19, 14 g of 2- (2-ethoxy-5-fluorophenyl) -2-tr | da1-methyl silylethanenitrile in 420 ml of a saturated ethanolic solution of hydrogen chloride is converted into a solid product — ethyl-1- (2-ethoxy-5-fluorophenyl - hydrochloride) 1-hydroxymethancarboxyl imidate (11.7 g, yield 81%), NMR.  (CDCl1), eL: 1.2-1.6 (2 triplets, 6H); 3.9-4.8 (2 quartets, 4H); 5.6 (singlet, W) | 6.8-7.3 {multigett, ZN  5- (2-Ethoxy-5-fluorofenyl). p1 sazolidin-2, 4-dione. According to Example 9 C, using chloroform as an extractant 11 g of ethyl i-2-ethoxy-5-fluorof nl 1-hydroxymethanecarboxy monidate hydrochloride is converted into 11.3 g of the crude product.  After recrystallization from isopropyl alcohol, purified 5- (2-ethoxy-5-fluorophenyl) oxazolidine-2,4-dione (7.8 g, t. square  188190 C). Calculated,%: C 55.23; H 4V21 | N 5.85.  C ,, H ,, Found,%: C 55.29; H 4.29; N. five. 91. ,,  Example 21   BUT.  2- (2-Mvtoksi-5-metsh1phenyl) -2trimetnlysiloksiztannitrnl.  According to Example 1A, 15 g (0.1 mol) of 2-label Si-5-methylbenzaldehyde in 300 ml of methylene chloride are introduced into the reaction with 19.8 g (0.2 mol) of trimethylsilylcarbonitrile in the presence of 200 mg of zinc iodide to give 2 g (2-methoxy-5-methylphenyl) -2-trimethylsiloxyethanenitrile in the form of an oil (24.7 g, yield 99%,), X (methylene chloride): 2899, 1613, 1497,1050 cm.  B. ETHIL-1-HYDROXY-1 (2-methoxy-5-metsh1fensh1) methanecarboxyimidate hydrochloride.  According to Example 1B, 24 g of 2- (2 methoxy-5-methylphenyl) -2-trimethylsiloxyethanenitrile in 500 ml of nESEL (ethanolic 1 solution of hydrogen chloride is converted into ethyl 1-hydroxy-1- (2-methoxy-5 4-methylphenyl) hydrochloride) -methaccrodcopic acid. 12.9 g, yield 52%, tons square  131-134 C, slight decomposition,).  C. 5- (2-Methoxy-5-methyl) oxazole.  din-2, 4-dione. According to Example 1A, but while stirring the reaction mixture for 16 hours at room temperature, before quenching 12.5 g (0.048 mol) of ethyl 1-hydroxy-1- (2-methoxy-5-methylphenyl) me- hydrochloride.  tankarboxyimidate in 1 liter of tetrahydrofuran is converted into 5- (2-methoxy-5-metip) oxazolidin-2.4 recrystallized from toluene (-dione (6.7 g, yield 63%,; R (ethyl acetate: chloroform 1: 1) " 0.51).  PRI me R 22.  A. 2- (5-Fluoro-2-methylphenyl) -2-trimethyl-n-oxo-tannanitrile.  According to npsoiepy 1 A, but while stirring the reaction mixture for 16 hours at a xi4nat temperature of 8.2 g (0.059 mol) of 5-fluoro-2-methylbenzaldegda in 200 mp of methylene chloride, was introduced into the reaction tank) with 8.9 g (0, 09 mol) of trimethylsilylcarbonitrile in the presence of zinc iodide (100 mg), resulting in 2- (5-fluoro-2-methylphenyl) -2-trmethylsiloxyethanenitrile in the form of an oil (13.6 g), 5WP (CDClj) shows the presence of peak 0, 2 m. d.  (protons of the trimethylsilyl group).  B. Chloro-1- (5-fluoro-2-methylphenyl) -1-hydroxymethanecarboxyHMugqata Hporohydrate.  According to Example 1B, except that the reaction is carried out for 1 hour at 13 g (0.055 mol) of 2- (5-fluoro-2-methylphenyl) -2-trimethylsiloxyethanenitrile. 408 ml of a valuable ethanol solution of hydrogen chloride is converted into solid ethyl 1- (5-fluoro-2-methylphenyl) 1-hydroxymethanecarboxyimidate hydrochloride (4.4 g), NMR (CDCIJ), o /, m. d. : 1.2 (triplet, EF); 2.4 (singlet, SN); 231 4.2 (quartet, 2H); 5.4 (singlet, 1H 6.7-7.4 (multiplet, GN).   WITH.  5- (5-Fluoro-2-met1shphenyl) oxazolidin-2, 4-dione.  According to example 21 C, but using 3.2 3 ec triethylamine 4 g (0 mol) ethyl 17 (5-fluoro-2-methyl phenesh1) -. 1-hydroxymethanecarboxyimidate is converted to crude 1 product (1.36 g).  After recrystallization from a mixture of 9; 1 carbon tetrachloride: chloroform obtained from 5- (5-fluoro-2-methylphenyl) oxazolindin-2, 4-dione (0.73 g, NMR shows the presence of approximately 10% of the impurity isomeric product.  Calculated,%: C 57.42; H 3.86; N 6.70 C eHiOjNF Found;%: C 57.22; H 3.55; N 6.66.  PRI and e r 23.  A. 2- (3 Fluoro-2-methoxy-5-methylphenyl) -2 - tr11methylssh1oxazanthanenitrile.  According to Example 22A, 0.5 g (3 mmol 3-fluoro-2 methoxy-5-methylbenzaldehyde in 23 ml of methylene chloride is reacted with 0.5 g (0.6 ml, 4.5 mmol) of trimethylsiloxane carbonitrile in the presence of zinc iodide (10 mg) resulting in 2- (3-fluoro-2-methoxy-5-methylfensch1) 2-trimetsh1Syloxyethanenitrile as an oil (0.49 g), NMR (methylene chloride) shows no aldehyde peak at 10 m. d.  B. Ethyl 1- (3-fluoro-2methoxy-5-methylphenyl) -t-hydroxymethanecarboxyimidate hydrochloride.  According to Example 22, 0.48 g (1.79 mmol) of 2- (3-fluoro-2-methoxy-5-methylphenyl) -2-trimethylsiloxyethanenitrile in 20 ml of a saturated ethanolic solution of hydrogen chloride is converted into ethyl 1- (3- fluoro-2-methoxy-5methylphenyl) -1-hydroxymethanecarboximide (0.36 g, t. square  105-10bS with decomposition).  WITH.  5- (3-Fluoro-2-methoxy-5-methylphenyl) oxazolidin-2,4-dione.  According to Example 22. Ethyl- 1- (3-fluoro-2-methoxy-5-methyl) -1-hydro1 {simethane-carboxyimidate is converted to 5- (3-fluoro-2-methoxy-5-methylphenyl) oxazolidine-2 which is recrystallized from toluene. , 4-dione (114 mg, t. square  138-139 C,).  Calculated Z: C 55.23; H 4.21; N 5.85.  C „Nzd" 04R 8 Found;%: C 54.77; H 4.15; N5.95.  Example 24; A. 2- (3-Chloro-5-fluoro-2-methoxyfesh1p) -2-trimesh1siloks etannitrile.  According to Example 23 A 1.5, g (8 mol) of 3-chloro-5-fluoro-2-methoxybenzaldehyde in 15 ml of methylene chloride and t react with trmemethylsilylcarbonitrile (0.95 g, 9.6 mol) in the presence of 15 mg zinc iodide, in terms of 2- (3-chloro-5-fluoro-2-methoxyphenyl) -2-trimetsh1 siloxyethane nitrile (2.13 g, 93% yield), X-ray (methylene chloride): 1600, 1587, 1464, 1121 cm. B. Ethyl 1- (3-chloro-5-fluoro-2-methoxyphenyl) -1-hydroxymethane-carboxyimidate hydrochloride.  According to Example 1 B, 2.1 g (7.3 mol) of 2- (3-chloro-5fluoro-2-meth, hydroxyphenyl) -2-trimethylsiloxyethanenitrile in 50 ml of a saturated ethanolic solution of hydrogen chloride is converted into ethyl 1- (3- chloro-5-fluoro-2-methoxyphenyl) -1hydroxymethanecarboxyl shdatat (1.74 g, yield 91%, tons square  132-134 C with decomposition), IR (KBG): 3125, 1653, 1481 cm-.  C. 5- (3-Chloro-5-fluoro-2-methoxyphenyl) -oxazolidine 2 j 4-dona.  According to Example 21 of C, 1.5 g (5.7 mmol) of ethyl 1- 3-chloro-5-fluoro-2-methoxyphenyl) -1-hydroxymethanecarboxyimidate hydrochloride are converted into 5- (3-chloro-5- fluoro2-methoxyphenyl) oxazolindin-2,4-dione (0.84 g, 57% yield, t. square  177-179 0) IR (KVg): 1748, 1709, 1477, 1377, 1170 cm.  P m and m 25.  A. 2- (2-: Ethoxy-6-fluorofensch1) -2trimethylsiloxyethanenitrile.  According to Example 1A, but when carrying out the reaction for 1 hour at room temperature, 1.3 g (7.7 mmol) of 2-ztoxy6-fluorobenzaldehyde in 30 ml of methylene chloride are reacted with 1.5 g (1.9 ml , 15.5 mmol) of trimethylsilylcarbonitrile in the presence of 30 t of zinc iodide to give 2- (2-ethoxy-6-fluorophenyl) -2-trimethylsiloxyethanenitrile as an oil (1.21 g), 7 (hexane: ethyl acetate 3: 1) .  B. Ethyl 1- (2-to-6-fluorophenyl) -1-hydroxymethanecarboxyimidate hydrochloride.  According to Example 5, 1.21 g of 2- (2-ethoxy-6-fluorofensch1) -2-trimethylsiloxyethanenitrile in 50 ml of a saturated solution of hydrogen chloride in ethanol is converted into ethyl 1- (2-ethoxy-6-fluorophenyl) - 1-hydroxymethanecarboxyimidate4 (0.61 g), NMR (CDCij) ,:, 6 (2 6H triplets); 3.8-4.8 (2 quartet, 4M) ;. 5.7 (singlet, 1H); 6.8-7.5 (multiplet, ZN).  WITH.  5- (2-Ethoxy-6-fluorophenyl) rxazolidin-2, 4-dione.  According to Example 22 C, but the reaction wire for 3 hours at room temperature, 0.56 g (2 mmol) of ethyl 1- (2-ethoxy-6-fluorophenyl) -1-hydroxymethane carboxyimidate hydrochloride in 55 ml of tetrahydrofuran is converted into a crude product.  After recrystallization from toluene, purified 5- (2ethoxy-6-fluorophenyl) oxazolidine-2,4-dione is obtained (t47 mg, t. PC.  127-128 С).  P r and m e p 26.  A. 2-Phenyl-2-trimethylsl1-oxyethane nitrile.  25 g (0.24 mol) of benzaldehyde are cooled in a bath containing a mixture of ice-water and 500 mg of zinc iodide is added to it.  28.5 g (0.288 mol) of trimethylsiloxycarbonitrile are added dropwise.  The reaction mixture is stirred at room temperature for 16 hours, diluted with 100 ml of chloroform, washed with three portions of an effective solution of sodium bicarbonate, 15consolidated, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness to give 2-phenyl2-trimethylsiloxyethanethitrile as an oil (46.1 g, 94% yield), Rj 0.60 (CHClj).  B, Hporohydrate ETHIL-1-HYDROXY-1phenylmethanecarboxyimidate.  According to IB, 46 g (0.22 mol) of 2-pheny 2-trimethylsiloxyethanenitrile in 750 ml of saturated ethanol solution of hydrogen chloride are converted to ethyl 1-hydroxy-1-pheny methancarboxyimidate hydrochloride (42.2 g, 89% yield, t . square  119-121С with decomposition).  The free base is obtained by distributing 20 g of the hydrochloride between 500 ml of methylene chloride and a 1N sodium hydroxide solution.  The methylene chloride layer is separated, washed twice with fresh portions of 1N sodium hydroxide, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness, yielding 826 ethyl 1-hydroxy-1-phenyl 1-methanecarboximidate (12.1 g, t. square  65-67 C).  WITH.  5-Phenyloxazolidine-2,4-dione.  According to Example 1 C, except that the reaction time is 16 hours at room temperature after passing phosghe. In the cold, 22 g (0.102 mol) of ethyl 1-hydroxy-1-phenylmethanecarboximidate hydrochloride is converted into 5-phenyl 1-oxazo-Lidine-2,4-dione recrystallized from toluene (10.5 g, t. square  103-105С).  Example 27  BUT.  2- (2,5-Dimethylphenyl) -2-trimethylsiloxyethanethanol.  According to Example 6A, but when the reaction is carried out for 64 hours, 10 g (0.075 mol) of 2,5-dimethylbenzaldehyde is reacted with 8.91 g (0.09 mol) of trimethylsilylcarbonitrile in the presence of 200 mg of zinc iodide, resulting in 2- (2,5-dimethylfensch1) -2trimethylsiloxyethanenitrile in the form of an oil (15.4 g, yield 88%, m / e 233). .  In "Chlororgtsrat ztil-1- (2,5-dimethylphenyl) -1-hydroxymethanecarboxyimidate.  According to Example 1, 16 g of 2- (2,5-dimethyl-phenyl) -2-trimethylsiloxy-tannanitrile is reacted with 350 ml of a saturated solution of hydrogen chloride in ethanol to obtain the solid product methyl ethyl-1- (2,5-dimethyl-phenyl) -1-hydroxymethylcarboxyimidate (12.8 g, yield 82%, tons  square  120122 С with decomposition, m / e 207).  WITH.  3- (2,5-Dimethylphenyl) oxazolidin-2, 4-dione.  According to Example 3 C and using methylene chloride as the solvent, 12.6 g (0.052 mol) of ethyl chloro hydrate-1- (2,5-dimethylphenyl) 1-hydroxymethanecarboxyimidate in 500 ml of methylene chloride is converted into 5-g recrystallized from toluene ( 2,5-dimethylphenyl) oxazolin-2,4dchone (5.82 g, t. square  134-136 With, in litas.  dan1l4 t. square  135-136 C).  PRI me R 28.  BUT.  2- (2-Nitrofensh1) -2-trimetshilosiloxyethanenitrile.  According to Example 1A, but with stirring for 2.5 hours at room temperature, 33 g (0.22 mol) of 2-nitrobenzaldehyde in 400 ml of methylene chloride are reacted with 43.4 g (55.3 ml, 0, 44 mol) tsh 1-methyl 1-carbonitrile in the presence of 125 mg of zinc iodide, resulting in 2- (2-nitrophenyl) -2-trimethylsiloxy-ethanethanol in the form of oil (54.7 g, yield 100%), NMR (methylene chloride ;, "l, shows the presence of peaks of 6.2 m d.  (singlet) and 7.4-8.3 m. d (multiplet), R (CHCIj) 0.75.  B, Ethyl-1-HYDROXY-1 (2-nitrophenyl) methancarboxy1 1Idate hydrochloride.  According to example 1B, but when the reaction was carried out for 1 h at 54.0 g (0.216 mol) of 2- (2-nitrophenyl) 2-trimethylsiloxyethane nitrile, it was reacted with a saturated solution of hydrogen chloride in ethanol (1400 ml) to obtain as a result, ethyl 1-hydroxy-1- (2-nitrophenyl) methanecarboxyimidate hydrochloride (49.4 g, yield 91.5%, tons square  135Pb c) NMR (CDCtJ, iT-: 1.0-1.5 m. d.  (triplet, ZN); 4.4-4.9 (quartet, 2H) 6.1 (singlet, 1H) j 7.5-8.2 (multiplet, 4H).  C. 5- (2-Nitrophenyl) oxazolin-2,4dione.  According to Example 22, 49 g (0.188 mol) of ethyl 1-hydroxy- (2-nitrophenyl) methanocarboxy siimidate hydrochloride is converted to 5- (2-nitro) oxazolidin-2, 4-dione (31.9 g, recrystallized from toluene). t. square  113115C), IR (methylene chloride): 1754, 1835 ctf.  Calculated,%: C 48.66; H 2.70; N 12.61.   Found,%: C 48.80; H 3.03; N 12.58.  PRI me R 29.  BUT.  2- (2-Methoxy-6-nitrophenyl) -2-trimethylsiloxyethanenitrile.  According to Example 1, 10 g (0.055 mol) of 2-methoxy-6-nitrobenzaldehyde in 250 ml of methylene chloride are reacted with trimethylsilylcarbonitrile (6.54 g, 0.066 mol) in the presence of 100 mg of zinc iodide, resulting in 2- (2 -methoxy-6-nitphenyl 2-trimethylsiloxyethanenitrile in the form of an oil (13.3 g, yield 86%, m / e 280) IR (methylene chloride): 1608, 1534, 1464,. 1361 cm is.  ETHYL-1-HYDROXY-1 (2-methoxy-6-nitrophenyl) methane-carboxy seimidate hydrochloride.  According to Example 5B, 13.1 g of 2- (2-methoxy-6-nitrophenyl) -2-trimethylsiloxyethanenitrile in 400 ml of a saturated solution of hydrogen chloride in ethanol are converted into ethyl 1-hydroxy-1- (2-methoxy-6-nitrophenyl) methanecarboxyimidate hydrochloride. (12.4 g, yield 91%, tons square  132-135C with decomposition), IR (KVg): 3175, 2899, 1681, 1639, 1527 cm Calculated,%: C 45.44; H 5.20; N 9.64.  C H OjNj-HCl Found: C 45.14; H 5.33; N 10.04.  WITH.  5- (2-Methoxy-6-nitrophenyl) oxazolidin-2, 4-dione.  According to Example 9 C, but using instead of 3.2 eq of triethylamine 3 eq. 12 g (0.041 mol) of ethyl 1-hydroxy-1- (2methoxy-6-nitrophenyl) methancarboxyimidate hydrochloride in 400 ml of tetrahydrofuran is converted into toluene recrystallized from 5- (2-methoxy-6-nitrophenyl) oxazolidin-2,4-dione (8.8 g, yield 86%, tons  square  1 1-183 C, m / e 252).  Calculated,%: C 47.62; H 3.20; N 11.11.  C. oVfiN Found,%: C 47.33; H 3.32; N 10.89.  Example 30  A. 2- (2,6-Difluorophenyl) -2-trimethylsiloxyethanethanol.  According to Example 1A, except that the reaction is carried out for 16 hours at room temperature, 9.1 g (0.064 mol) of 2,6-difluorobenzaldehyde in 100 ml of methylene chloride are reacted with 7.13 g (0.072 mol) of trimethylsilylcarbonitrile in the presence of 100 mg of io-zinc, resulting in the result of 2- (2,6-difluorophenyl) -2-trimethylsiloxyethanenitrile in the form of an oil (14.34 g, yield 93%); X (methylene chloride): 1626, 1600, 1471, 1190 1081 cmH B. Ethyl 1-hydroxy-1 (2,6-difluorophenyl) methanecarboxyimidate hydrochloride.  According to. Example 1B except that the reaction is carried out for 1 hour at 0 ° C, 14.3 g (0.059 mol) of 2- (2,6 difluorophenip) -2-trimethylsiloxyethanenitrile in 300 ml of a saturated solution of hydrogen chloride in ethanol in ethyl-1-hydroxy hydrochloride | (2,6-difluorophenyl) methanecarboxyimidate (13.1 g, yield 88%, t. square  135137 With decomposition, m / e 215).  Calculated,%: C, 47.72; H N 5.57.  C oHiiOjNFjHCl.  Found,%: C 47.32; C 4. 73; And 5.56.  C. 5- (2,6-Dipherrphenyl) oxazolidin2, 4-dione.  According to Example 29. C, 12 g (0.048 mol) of methyl 1-gldro1ssi-T- (2,6-difluorophenyl) methanecarboxy-seimidate hydrochloride in 500 ml of tetrahydrofuran is converted into a crude product.  The latter recrystallizes approximately 60 ml of isopropanol, resulting in a purified 5- (2,6-difluoro-phenyl) oxazolin-2, (5.8 g, 57% yield, t. square  196-198 C, m / e 213) IR (KBG): 3175, 1812, 1739, 1361, 1152 cm :.  Example HCC A.  2- (3-Hpor-6-methoxy-2-methylphenyl) -2-trimethylsil6xyethylenetri.  In Example 1 A, except that the reaction was carried out for 4 days at room temperature, 840 Kg, (4.5 mmol) of 3-chloro-6-methoxy-2-nethyl benzaldehyde in 25 ml of methylene chloride were reacted with trimethylsilylcarbonitrile ( 535 mg, 5.4 mmol in the presence of zinc iodide (10 mg), resulting in 2- (3-chloro-6methoxy-2-methylphenyl) -2-trimethylsiloxyethanenitrile.  Example 32  The sodium salt of 5- (5-chloro-2-methoxyphenyl) oxazolidine 2,4-dione.  5.0 g of 5- (5-chloro-2-methoxyphenyl) oxasolidine-2,4-dione is dissolved in 200 ml of methanol and a solution of 830 mg of sodium hydroxide in 25 ml of methanol is added to the resulting solution, after which the resulting mix for 1 min at room temperature.  While stirring, 1.25 l of ether is added to the mixture to precipitate the desired product (4.56 g, t. square  224-226 0 with decomposition.  After recrystallization of absolute alcohol of ethyl alcohol and isopropyl ether, purified sodium salt of 5- (5-chloro-2-methoxyphenyl) oxazolidin-2, 4-dione is obtained (4.07 g, t. square  224-22b C with decomposition).  Calculated,%: C, 41.32; H 3.47 {N 4.82 C gH 04NCINa1.5 Found: C 41.56; H 3.22; N 4.97.  Example 33  Sodium salt of 5- (2-chloro-6-methoxyphenyl) oxazolin 2, 4-dione.  When heated to 22.5 g (0.098 mol) of 5- (2-chloro-6-methoxyphenyl) oxazolidine-2,4-dione, it is dissolved in 300 ml of ethyl acetate and 200 ml of tetrahydrofuran and clarified by filtration. n 35 ml of tetrahydrofuran for nepe nasal to filter and rinse.  The mother liquor is diluted at room temperature with 100 ml of ethyl acetate and 1–6 db of 5.06 g (0.094 mol) of methyl | Ta sodium in 25 ml of methanol.  Water (4.8 ml) is added to the reaction mixture and crystallization is carried out; caused by the introduction of embryo or tapping on the walls of the vessel.  After granulating for 4 hours by filtration, 21 g of salt is obtained.  After second mixing in a mixture of 200 ml of ethyl acetate and 5 ml of water, a purified 5- (2-chloro-6-methoxyphenyl) oxazolidin-2, 4-dione sodium salt (19.6 g, t. square  96-98 C).  Calculated,%: C 40.08; H 3.70; By 7.67; Ct 11.83; HjO 12.02.   H O NCtNa- 2 HI) Found, Z: C 39.92; H 3.89; N 4.75; Na 7.81; Cf 11.59; 11.69.  The water is removed by drying under vacuum for 3 hours at.  Calculated,%: C, 45.56; H 2.68; N5.31; Na 8.72; C {13.45.  . C H O NClNa Found,%: C 45.11; H 3.06; N 5.27; Na CI 12.89.  6.86 g of the free acid was isolated from the mother liquor as a result of partial distillation of the solvent, extraction with excess sodium hydroxide and addition of the main extract with 6N hydrochloric acid.  Example 34  3-Acetyl-5- (5chloro-2-methoxyphenyl) oxazolidin-2,4-: dione.  Method A.  1.21 g (5 mmol) of 5- (5chloro-2-methoxyphenyl) oxazolidine-2,4-dione are suspended at room temperature in 25 ml of 1,2-dichloroethane.  To the suspension, 505 ml (0.7 ml, 5 sholes) of triethylamine are added and the resulting mixture is stirred for 1 minute until a solution is obtained.  393 mg (0.36 ml, 5 mmol) of chloro are added to it, the mixture is stirred and the resulting mixture is stirred for: 1 h.  The reaction mixture is then concentrated to a volume of 5 ml and the solid phase is evaporated by the addition of 25 ml of ether.  The precipitated solid phase is distributed between chloroform and saturated sodium bicate solution.  The organic phase is separated, washed with fresh sodium bicarbonate solution and brine, dried over anhydrous magnesium sulphate -and otr (Htfl | o. t solvent, giving 3Aceti -5- (5-hyor. -2-methoxyphenyl) oxaeolidan-2, 4-dione (910 mg, yield; (64%, {m. square  161-164 C),. NMR (tCO-b), L2.5 (singlet, GN); 3.9 (singlet, SN); 6.0 (singlet, 1H); 7.4 (multi plet, 3N),.  .  According to the specified. when replacing acetyl chloride with an equivalent amount of 5- (5-chloro-2-methoxyphenyl) oxazolidide isobutyryl chloride, 2,4-dione was converted to 5- (5-chloro-2methoxyphenyl) -3-isobutyryoxaiderol-2, 4-dione .  Method B.  100 mg of 5- (5-chloro-2-methoxyphenyl) oxazolidine-2,4-dione is dissolved in 2.5 ml of tetrahydrofuran and an excess of acetic anhydride (4 drops) is added to the solution, after which the reaction mixture is left at room temperature temperature for 16 hours  After the solvent is distilled off to dryness, I get 3-acetyl-5- (5-chloro-2-methoxyphenyl) o sazolidin-2, A-dione.  R 0.75 (ethyl acetate: chloroform 1: 1), t. square  160162 C.  Example 35  5- (5-Chloro-2-me, toxiphenyl) -3-cyclohexylcarbamoyloxazolidin-2, 4-dione.  1.21 g (5 mmol) of 5- (5-chloro-2-methoxyphenyl) oxazolidine-2,4-dione are suspended in 50 ml of 1,2-dichloroethane.  To the resulting suspension was added 1 drop of triethylamine and 626 mg (5 mmol) of cyclohexyl isocyanate.  The reaction mixture is then stirred for 19 hours at room temperature, successively dilute the portions of a 1N sodium hydroxide solution, two portions of the 1N hydrochloric acid solution and one brine, dry over anhydrous magnesium sulfate, filter and concentrate.  After recrystallization from toluene, purified 5- (5-chloro-2-methoxyphenyl) -3-cyclohexylcarbamoyloxazolidine-2,4-dione (435 mg, t. square  150-153 ° C), IR (KVg): 1813, 1761, 1527, 1493, 1364 cmL Example 36.  5- (5-Chloro-2-me1CH5xyphenyl) -3-ethoxycarbonyloxazole, 4-dione.  1.32 g (5 mmol) of 5-5-chloro-2-methoxyphenyl-oxazolidine 2,4-dione sodium salt, prepared in accordance with Example 118, is suspended in 50 ml of toluene.  708 mg (5 mmol) of ethyl chloroformate are added to the reaction mixture and heated under reflux for 4.5 hours, then kept at room temperature for 18 hours, clarified by filtration, and concentrated to an oily residue.  The oil is crystallized by trituration with a small amount of ether (1.02 g) and recrystallized from a mixture of ethyl acetate and goxane to obtain purified 3-ethoxycarbonyl-5- (5-chloro-2methoxyphenyl) -3-ethoxycarbonyloxazolidin-2, 4-dione (920 mg , yield 59%, t. square  100-103 C, m / e 3. 15/313).  Calculated,%: C 49.77; H 3.86; N 4.47.  C, Found,%: C 49.99; H 4.00; Example 37  3-Acetyl-5- (2chloro-methoxyphenyl) oxazolidin-2,4dione.  1.21 g (5 mmol) of 5- (2-chloro-6-methoxyphenyl) oxazolidine-2,4-dione paclori in 10 ml of tetranidrofuran and added to the resulting solution of 613 Mt (0.57 ml, 6 mmol) acetic anhydride, then the solution is stirred at room temperature for 44 hours  The reaction mixture was concentrated to oily and partitioned between chloroform and saturated sodium bicarbonate.  The chloroform layer is washed with a fresh portion of sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to a dry residue.  After repeated agitation of the residue with 50 ml of ether, 3-acetyl5- (2-chloro-6-methoxyphenyl) oxazolidine 2, 4-dione (790 mg, 56%, t.) Is obtained. square  132135 С, m / e 285/283).  Example 38  5- (2-Chloro-6-methoxyphenyl) -3-methylcarbamoshoxazolidin-2, 4-diov.  1.21 g (5 mmol) of 5- (2-chloro-6-methoxyphenyl) oxazolidine-2,4-dione is suspended in 25 ml of 1,2-dichloroethane, 1 drop of triethyl amine and 285 mg (0 , 29 ml, 5. mmol) methyl isocyanate, then stirred for 3 h at room temperature, the result is a solution.  The reaction mixture is diluted with 50 ml of 1,2-dichloroethane, washed with two portions of saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated to obtain the desired product.  After recrystallization from a mixture of chloroform and hexane, purified 331 5- (2-chloro-6-methoxyphenyl) -3-methylcarbamoyloxazolidin-2, 4-dione is obtained (1.04 g, yield 70%, t. square  124-127c with decomposition, m / e 300/298), PRI me R 39.  5- (2-Chloro-6-methoxyphenyl) -3-ethoxycarbonyloxazolidin-2, 4-dione.  542 mg (2.06 mmol) of anhydrous sodium salt of 5- (2-chloro-6-methoxy-feil) -oxazolidine-2,4-dione, prepared according to Example 33, and 291 mg (2.68 mmol) of ethyl chloroformate are mixed with -20 ml toluene and heat the reaction mixture under reflux for 3 hours, then cool to room temperature and stir for another 16 hours, after which the solvent is evaporated to dryness, to obtain a residue weighing 415 mg.  The residue was recrystallized from UT from Toluene, resulting in a pure 5- (2-chloro-6-methoxyphenyl) -3 ethoxycarbonyloxazolidin-2, 4-dione (212 mg, t. square  196-200 ° C).  Example 40  Separation of 5- (5-chloro-2-methoxy) oxazolidin-2, D-dioHa into optical isomers.  1.20 g (5 mmop) 5- (5-chloro-2methoxy) oxazolidin-2,4-dione n 1.47 g (5 mmol) L-quinidium (tiJu-109.2) is dissolved at reflux. in 10 m of ethanol.  For cooling at room temperature (d, room temperature crystallizes with the salt (1.23 g, t. square  142-144 ° C), (ethanol) -58.6 °).  The solid residue is retained, and the mother liquor is distributed between ethyl acetate and 1N hydrochloric acid solution.  The organic layer is dried over anhydrous magnesium sulphate, filtered and the Ut is distilled off the solvent to dryness (520 mg).  The resulting residue is taken up in 20 ml of methanol and recrystallized by the addition of 30 ml of water.  After 20 minutes, the first batch of product is obtained (157.4 ml, t. square  177.51790c), Cijj) (ethanol) -6.6 °).  The second portion of the product isolated from ma. the exact solution is a (-) - 5- (5-chloro-2-methoxy) oxazolidine 2,4-dione, which has a frequency degree (based on optical isomer) of 73%.  After recrystallization of 50 mg of this product from 1 ml of methanol and 1.5 ml of water, a product having a purity by optical isomer is obtained. . , equal to 85% (25.4 mg, tons square  164-166 0), and: D (ethanol) -22.24).  8 The previously stored solid salt is decomposed by distributing between chloroform and 1N hydrochloric acid solution, after obtaining after distillation of the solvent from the dried layer in the oroform 0.488 g of solid residue; This residue is taken up in 20 ml of methanol and recrystallized (with the addition of water (+) - 5- (5-chloro-2-methoxy) oxazolidine.  The product is obtained in two portions: first (182.4 mg, t. square  173-174,), Sd (ethanol) 4: 26.66 and the second (103 mg, t. square  171-174C), (ethanol) + 27.06 °.  After recrystallization of 59 mg of the first portion of the product from t ml of methanol and 1.5 ml of water, a product with a slightly increased rotational capacity (40 mg, t. square  171.5173 С) ,, (ethanol) + 26.9b.  The study of the product with rotational ability by NMR using Tris-f3- (heptafluoropropylgly Dopximethylen) -d -camphoratatJ-Evropi (III) shows that a product with a rotational capacity equal to -f 27.06 is an optically pure isomer at 100%.  Example 41  BUT.  2-, (2-Methoxy-1-naphthyl) -2-trimethylsiloxyethanenitrile.  According to Example 3A, but using ether instead of methylene chloride, 25 g (0.134 mol) of 2-methoxy-1-naphthaldehyde in 100 ml of ether is reacted with 15.8 g (0.16 mol) of trimethylsilylcarbonitrile in the presence of zinc iodide. (0.266 g), resulting in 2- (2-methoxy-1-naphthyl) 2-trimethyl ethyl oxanenyl in the form of a solid product (36.7 g), NMR (CDCI-): iO, 2 (singlet, 9H); 3.9 (singlet, SN); ; 6.6 (singlet, 1H); 7.0-8.0 (multiplet, 6th).  AT.  Ethyl 1-hydroxy-1- (2-methoxy 1-naphthyl) methanecarboxyimidate.  According to Example 4B, 36.7 g (0.128 mol) of 2- (2-methoxy-1-naphthyl) -2-trimethylsiloxyethanethiene are not: converted to ethyl 1-hydroxy-1- (2-methoxy-1-naphthyl) methane carboxydish (33 . g, oil), NMR (SOS |: 5), L: 1.0 (triplet, 3N); . 3.8-4.3 (quartet and singlet, 5H); 6.0 (singlet, 1H); 7.0-8.1 (multi plet, 6H).  : C, 5 (2-Methoxy-1-naphthyl) oxazolium-2, 4-dione.  According to Example 4 C, for acKJH04eHHeM of that not 2.0, but 2.3 eq of triztilamine is used, 16.5 g (0.063 mol) of ethyl 1-hydroxy1- (2-methoxy-1-naphthyl) methanecarboxyl imidate in 500 mL of tetrahydrofuran is recovered in the crude product.  After recrystallization from a mixture of ethyl acetate and toluene, purified 5- (2-methoxy-1-naphthyl) oxazolidin-2, 4-dioi is obtained in two portions (7.7 g t. square  199-201c), IR (KVg): 1820, 1740 cm Calculated,%: C 65.37; H 4.31; N 5.44.  Cl4H-. i% N Found: C 65.40; H 4.45; And 5.40.  Example 42  A. 2- (2-Ethoxy-1-naphthyl) -2-tri-ethylsiloxy-ethynitrile.  According to Example 41 A, 4.5 g (22.5 mmol) of 2-ethoxynaphtaldehyde in 50 ml of ether are introduced into a reaction with 2.6 g (27 mmol) of trimethylsilane. bonitrile in the presence of zinc iodide (50 mg), resulting in 2 - 2-ethoxy-1-naphthyl) 2-trimethylsnloxy-ethynitrile in the form of oil (g), NMR (CDCl), A: 0.2 (singlet, 9H) ; 1.4 (triplet, 3N); 4.0 (quartet, 2H); 6.5 (singlet, 1H) 7.0-8.0 (cartoon, 5H); 8.5 (synget, 1H). .  B. Ethyl-1- (2-ethoxy-1-naphthyl) -1-hydroxymetacarboxyimidate (hydrochloride).  According to Example 1, 5.8 g, (19.3 mmol) of 2- (2-ethoxy-1-naphthyl) -2 trimethylsiloxyethanenitrile in 140 ml of ethanol, saturated with hydrogen chloride, are converted to ethyl 2-ethoxy-1-acetic hydrochloride. ) -1-hydroxymethanecarboxyimndate (5.0 g, t. square  110112 C).  e.  6- (2-Ethoxy-1-naphthyl) oxazolidin-2,4-dione.  Accord: clear example 1C,. but when carrying out the reaction for 64 hours at room temperature after passing phosgene in the cold, 5.0 g of X16.1 linne) ethyl 1- (2-ethoxy-1-naphthyl) -1-hydroxymethanecarboxyimidate hydrochloride in 200 ml of tetrahydrofuran is converted into recrystallized Mbrit from toluene 5- (2-ethoxy-1-naphthyl o "sazoldin-2,5-dione (0.57 g, t. square  221-224 С, m / e - 271).  Example 43  BUT.  2- (2-Benzyloxy-1-naphthyl) -2trimethylsiloxyethanenitrile.  According to Example 41A, but when the reaction is carried out for 48 hours, 9.0 g of CO, 034 mol of 2-bizyloxy-1-naphthaldehyde in 80 m of ether are reacted with 4. 0 g 88 (0.041 mol) of trimethylsilylcarbonitri la la. the presence of about 65 mg of zinc iodide, resulting in 2- (2-benzyloxy-1-naphthyl) -2-trimvtil "siloxyethane nitrile in the form of a viscous oil (10.0 g), NMR (CDClj)," i: 0.2 (singlet, 9H); 5.2 (singlet, 2H); 6.6 (syn gl, 1H); 7-8,4 (mouse, 11H).  AT.  Hydrochloride ethnl-1-. (2-benz1Shyksi-1-naphthyl) -1-hydroxymethanecarboxyimimidate.  According to example 1, 5.0 g (0.014 mol) of 2- (2-benzylbksy 1-1 -1a and ts1) -2-trimethylsiloxyethanethanitrile, and in 190 ml of a valuable solution of hydrogen chloride in ethanol, is converted into solid hydrochloride, ethyl-1- ( 2-benzyloxy-1-naphthyl) -1-hydroxymethanecarboxyimidate (4.0 g), NMR (DMSO), A: 1.0 (triplet, 3H) j 4.2 (quartet, 2H) j 2.5 (steglet, 2H) ; 6.4 (singlet, 1H); 7.2-8.2 (multiplet, 11H).  WITH.  5- (2-Benzyloxy-α-naphthyl) oxazolidin-2, 4-dione.  According to Direct 9 C, with the exception that instead of 3.2 equivalents of triztilamine, 2.1 equivalents are used, 4.0 g (0.011 mol) of ethyl 1- (2-benzyl 1cc-).  1-naphthyl) -1 -hydroxymethancane: ribboximidate in - 180 ml of tetragdcrytropha and converted into 5- (2-benzylO1CCI-1-naphthyl), oxazolidin-2, 4-dione (1j61 r, t, recrystallized from toluene). square  197-199 C).  C, 72.06; H 4.54; Calculated,%: N 4, go.  C.  Found,%: C 71.94; H 4.60; N 4.22.   P r and m  e 44.  BUT.  2- (2-Fluoro-1-naphthyl) -2-trimetsh | - siloxyetheinitrile.  According to Example 1A, 2.0 g (11 mmol) of 2-fluoro-1-naphthaldehyde in 80 ml of methylene chloride was introduced into the reaction with 1.4 g (1.8 ml, 14 mmol) of trimethylsilylcarbonitrile in the presence of 20 mg of zinc iodide. resulting in 2- (2-fluoro-1-naphthyl) -2-Tr1 | etylsiloxy-tannitrile as an oil (2.7 g), R 0.62 (CHCIj).  2.7 g, 2- (2-fluoro-1-naphthyl) -2-trimethylsiloxyethanenitrile is dissolved under OC in 85 ml of saturated with hydrogen chloride ethanol and stirred for 1 hour at the same temperature.  The reaction mixture is distilled to dryness and triturate the resulting residue with ether to obtain ethyl 1- (2-fluoro 1-naphthyl) 1 hydroxymethane carboxyimidate (2.4 g) ,. NMR (DMSO): 1.2 (triplet, EF); 4.6 (quartet, 2H); 6.5 (singlet, IH); 7.4-8.4 (multiplet, 3N); 4.6 (quartet, 2H) 6.5 (singlet, 1H); 7.4-8.4 (multiplet, 6H), C.  5- (2-Fluoro 1-naphthyl) oxazolidin-2, 4-dione.  According to Example 3, except that the reaction time is 16 hours after passing phosgene and that 3.3 equivalents of triethylamine are used, 2.4 g (8 mmol) of ethyl 1 - (2-fluoro-1-naphthyl) 1-hydroxymethancarboxyimidate in 150 ml of tetrahydrofuran is converted to 5- (2 fluoro-1 naphthyl) oxazolidin-2 recrystallized from toluene (1.63 g, t. square  153 154 C) For D-analysis, the product is recrystallized once more from toluene (1.15 g, t. pl, 152-154 ° C) Calculated,%: C 63.69; H 3.29; N 5.71, C. HgOjNF Found,% gC 63.69-H 3.29; N.  5.71, P m and m 45.  BUT.  2 (2 - Methyl 1 naphthyl) -2 - tri-methylsiloxyethanol.  According to 1A, except that the reaction is carried out for 12 hours at room temperature, the reaction is carried out between 0.52 g (3 mmol) of 2-metsh1-1-, naphthyldehyde in 2Q ml of methylene chloride, and 0.40 g (3, 9 mmol) of trimethylsilylcarbonitrile in the presence of 10 zinc iodide to obtain 2- (2 methyl-1 naphthyl) -2-trimethylsyl1-ethane nitrile (0.71 g), R 0.35 (chloroform).  at.  Ethyl-1-hydroxyI 1 (2-methyl-1-naphthyl) methancarboxyamide hydrochloride date.  According to Example 5B, 0.71 g (2.6 mmol) of 2- (2-methyl-1-naphthyl) -2. trimethylsiloxyethanenitrile in 25 ml of saturated with hydrogen chloride, ethanol is converted into ethyl chlorohydrate-1-hydroxy-1- (2-methyl-1-naphthyl) methane carboxyimide (0.48 g), NMR (DMSO: 1.2 (triplet, GN) ; 2.7 (ZN singlet); 4.5 (quartet, 2H); 6.5 (singlet, 1H); 7.2-8.4 (multiplet, 6H).  WITH.  5- (2-Methyl-1-naphthyl) oxazolidide IN-254-DION, According to Example 44 C, 0.47 g (1.9 mmol) ethyl 1-hydroxy 1- (2-methyl 1-naphthyl) metacarboxyimidate hydrochloride 30 ml of tetrahydrofuran are converted to 5- (2-methy-1-1-naphthyl) oxazolidin-2, 4-dione (185 mg, t) recrystallized from toluene (185 mg, t. pl, 145-147C, m / e 24f).  After lane. crystallization from a mixture of hexane and ether receive a sample for analysis (t. square  147-150 ° C).  Calculated,% g C 69,72; H 4.60; K 5.80.  WITH. . . . .  Found,%: C 69.79; H 4.87 N 5.74, PRI me R 46.  A, 2- (2,6 Dimethoxy-1-naphthyl) 2 trimethylsiloxyethanenitrile, According to example 9.  A 2j3 g (10.6 mmol) 2,6 dimethox-1-naphthaldehyde in BO ml. The ester is introduced into the reaction with 1.2 g (12.7 mmol) of trimethylsilylcarbonitrile in a prix. 50 mg of zinc iodide, resulting in solid 2- (2,6-d1-shetaxgr-1-naphthyl) -2 trimethyls. iloxyethane nitrate (3.5 g), Rf 0.75 (chloroform g ethyl acetate 1: 1), in the NMR spectrum (ether) there is a 6.8 m face, e.  (g /), B, Ethyl-1- (25b-d1-1methoxy-1-naphthyl) 1 hydroxyl etancarboxeshdat).  According to Example 1 B and 4 B (Method A), except that the reaction takes 2.5 hours. at 0 ° Cj, 3.3 g (10 mmol) of 2- (2.6 dimethoxy - 1-naphthyl) 2 Tp methylsiloxy ethaconitrile in 100 ml of a saturated solution of hydrogen chloride in ethanol is converted into ethyl 1 (2 J b-dimethoxy 1-naphthyl) -1-hydroxymethanecarboxyimidate, obtained as an oily product (3.2 g), NMR (CDCl 3), (trc. Plet, ZN); 3.9-4.4 (multiplet, 8H): 6.0 (1H singlet); 7.0-8.2 (multiplet, 5H), C, 5- (25b-Dimetski-1-naphthyl) oxazolid. , 4-t1; ion According to Example 4 (method A), 3.0 g of eT1-Sh-1 - (2, 6-dimethoxy-1-naphthy, p) -1-hydroxymethanecarboxyimidate in 125 ml of tetrahydrofuran is converted into the desired product.  To isolate it, the reaction mixture is slowly poured onto 200 mg of crushed ice and extracted with two portions of 100 ml of ethyl acetate.  The combined extracts are dried over anhydrous 5% magnesium sulphate, filtered, from: The solvent is thinned to form a 1-half semi-solid residue (2.6 g), which is 1 Crystallized by trituration with ether, resulting in 5- (25bdimetho-x-1 -naphthyl) oxaz olydin-2,43911 ftUOH (0.43 G, T. Submarine  175-180C, M / e 287).  Example 47  A.  2- (7-Fluoro-1-naphthyl) -2-trimethyl siloxyethanenitrile.  4.7 g (0.026 mol of 7-fluoro-1-naphthaldegilg in 150 ml of methylene chloride are reacted with 3.4 (0.033 mol) of trimethylsilylcarbonitrile in the presence of 50 mg of zinc iodide according to example 7, to give 2- (7-fluoro- 1-naphthyl) -2-trimethylsiloxyethanenitrile in the form of a solid (6.2 g), NMR (CDCIj), (A:, 0.2 (singlet, 9H); 6.0 (singlet, 1H); 7.2 - 8, O (multiplet, 6H).  According to example 1 B, but when prodedii reaction in t. For 3 hours at 6.2 g of 2- (7-fluoro-1-naphthyl) -2trimethylsiloxyethanenitrile in 200 ml of ethyl alcohol saturated with hydrogen chloride, they are converted to ethyl 1- (7-fluoro-1-naphthyl) -1-hydroxymethanecarboxyimidate hydrochloride (6.6 g, t. square  135-138 0, NMR (CDCI,), “f-: 1.2 (triplet, 3N); 3.9-4.2 (quartet, 2H) 5.6 (singlet, 1H); 7.2-8.0 (multiplet, 6H).  WITH.  5- (7-fluoro-1-naphthyl) -oxazolidin-2, 4-dirn.  According to Example 44. C, 6.6 g (0.025 mol) of etl1-1 (7-fluoro-1-naphthyl) -1-hydroxy-imidag hydrochloride are converted to 5- (7-fluoro-1-naphthyl) ox sazolidin-2,4-dione (3.07 g, t. square  147-150 C).  Calculated,%: C 63.69; H 3.29; N 5.71.  C HgOjNF.  Found 2: C, 63.49; H 3.45; N5.75.  Example 48  : BUT.  2 (4-Fluorophenyl) -2-trimethylsiloxyethanenitrile.  20 g (0.16 mol) of 4-fluorobene apdehyde and 200 mg of chocolate are mixed with 100 ml of ether and the mixture is cooled to 0-5 ° C.  19.1 g (0.19 mol of trimethylsilylcarbonitrile) are added dropwise to it and the reaction mixture is stirred overnight.  It is then diluted with 100 ml of ether and the product continues to be isolated according to Example 1, resulting in 2- (4-fluorouféyl) -2-trimethylsiloxyethanenitrile in the form of an oil-like liquid (31.7 g).  AT. Ethyl -1-4- {fluorofensh4: | -hydroxymethanecarboxyimidate hydrochloride.  So40.  According to Example 1, 31.7 g (0.142. Mol4) 2- (4-fluorofensch1) -2-trimethylsiloxyethanenitrile is introduced into the reaction in 750 Mp of an exemplary solution of hydrogen chloride in ethanol, resulting in etsh1-1- (4-fluorophenyl) 1-hydroxymethancarboxyimidate hydrochloride (33.8 g, t . square  131-133 C), NMR (DISO), 1.2 (triplet, 3N); 4.6 (quartet 2H); 5.8 (singlet, 1H); . 7.0-7.7 (multiplet, 4H).  WITH.  5- (4gFluorophenyl) oxazrlidine-2, dione.  According to Example 1 C, with the exception that the reaction is carried out for 48 hours at room temperature following the passage of phosgene, 33.1 g (0.14 moles) of hydrochloride.  ethyl-1-C4-fluorophenyl) -1-hydroxynetanecarboxyimidate in 1200 ml of tetrahydrofuran is converted to 5- (4-fluorofvnil) -1 oxazolidin-2,4-dione recrystallized from toluene (13.5 g, t. square  154-1550С), NMR (DMSO),: 6.05 (singlet, 1H); 7.0-7.7 (multi-i plet, 4H).  Calculated,%: C 55.40; H 3.09 {N 7.17.   Found,%: C 55.29} H, 3.40; N 7.29.  The second portion of the product is obtained from toluene, used for nepdcrystallization (g, t. square  137140 C).  5- (2-Methoxy-3,6-difluorophenyl) -oxazolidin-2, 4-dione can also be prepared according to the invention.  This connection has t. square  103-104 C and the following spectral data: MS: 243 (M, 100%); 127 (97Z); 126 (47; t); .  250 MHz NMR; (D-DMSO): delta 7.50 (t, 1H); 7.20-7.10 (t, 1H); 6.62 (S ,.  1H); 3.90 (3N, J - 1 Hz).  The hypoglycemic activity of oxazolidin-2,4-diones when testing deviations in the glucose content in the blood of rats (H) is given in Table.  1, Hyp-glycemic activity of oic "sazolidin-2, 4-dioiov when testing for deviations in blood glucose RATS is presented in TA.  2  Hypoglycemic activity of 5- (2-.  methoxy-3,6-difluorophenyl) -oxazole to 1H2, 4-dione, determined in the experts, by definition, the effect of glucose on rats, is given in Table.  3
4.1
Table 1
42
112D888
Continued table. one
  1124888
Tab. T
44
Continued table 2

权利要求:
Claims (1)
[1]
The method of obtaining derivatives
5-substituted oxazolidin-2,4-diones of the general formula I where is a hydrogen atom, acetyl,
C ^ -Cj-alkylcarbamoyl, cyclohexylcarbamoyl or Cj-C ,, alkoxycarbonyl;
R-2 is a group of the formula where Z ₁ is a chlorine atom or trifluoromethyl;
Z ^ - chlorine atom, methyl, C., - Cy-alkoxyl, nitro group or trift ^ rmethyl;
Z ₃ is hydrogen or halogen, methyl or Cf-Cj alkoxyl;
~ a hydrogen or halogen atom, methyl, nitro group or alkoxyl, provided that when R ₃ is a hydrogen atom, Z ^ is different from the p-atom of the hydrogen atom, and Ζ _χ and Z ₄ together are not methyl;
Z ₅ is a hydrogen or fluorine atom, or a nitro group;
Y, is a hydrogen or fluorine atom, methyl, C _p -C ^ -alkoxyl or benzyloxy group;
Y ₂ is a hydrogen atom or methoxy, in the form of a racemate or an optically active isomer in free form or in the form of a pharmaceutically acceptable salt, when R is a hydrogen atom, characterized in that the compound of general formula II
BUT NH where Rj has the indicated meanings;
R $ - C γ-Cj-alkyl, <
subjected to interaction with phosgene in an inert organic solvent and the resulting compound’’s General formula III
SU „1124888
Z _S ύ ₂ where they have the indicated meanings, they are hydrolyzed to obtain a compound of the general formula I, where R ^ is a hydrogen atom, and, if desired, the racemic compound of the general formula I, where R, is a hydrogen atom, is separated into its optically active isomers by separating the diastereomeric salts formed with optically active amine, and liberating the optically active isomer by acidification, or acylated connected of general formula I, wherein R _n - a hydrogen atom, an acid chloride of the corresponding acid anhydride ,, or a corresponding isocyanate with Acquiring a compound of general formula I, wherein R ^ C C j- (alkylcarbamoyl, cyclohexylcarbamoyl FPI C ^ C ^ alkoxycarbonyl, and the desired product was isolated as a racemate or an optically active isomer in the free form or in pharmaceutically acceptable salt form.

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同族专利:

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公开号 | 公开日

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CS244946B2|1986-08-14|

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PL131526B1|1984-11-30|

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PL232329A1|1982-10-25|

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CS564581A2|1985-09-17|

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PL237147A1|1982-12-20|

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SU1099843A3|1984-06-23|

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PL131530B1|1984-11-30|

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CS244901B2|1986-08-14|

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CS904483A2|1985-09-17|

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PL237146A1|1982-12-20|

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PL131452B1|1984-11-30|

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CS904383A2|1985-09-17|

---

SU1184442A3|1985-10-07|

---

CS244947B2|1986-08-14|

---

US4342771A|1982-08-03|

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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US06/222,202|US4367234A|1980-07-28|1981-01-02|Hypoglycemic 5-substituted oxazolidine-2,4-diones|

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