• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Reaction of a 5-substituted resorcinol with a ketal of 4-(1-hydroxy-1-methylethyl)-3-cyclohexen-1-one in the presence of a suitable catalyst effects condensation to provide substantially exclusively a cis-1-hydroxy-3-substituted-6-6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H- dibenzo[b,d]pyran-9-one.
    公开号:SU778712A3
    申请号:SU782632856
    申请日:1978-07-06
    公开日:1980-11-07
    发明作者:Беван Блэнчард Вильям；Вильбур Риан Чарльз
    申请人:Эли Лилли Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    KIM, as 1,2-ethanediol, 1,3-propandiol, 2,2dimethyl-1, 3-propandiol, 2-methyl-2-ethyl1, 3-propandiol or 2,2-diethyl-1,3-propandiol, in in the presence of an acid such as para-toluenesulf. acid, to obtain the corresponding ketal 4-meth, hydroxycarbonyl-3-cyclohexen-1-one of formula (2).
    Usually, target products are not needed for further purification, but, if desired, they can be distilled or pro-chromatographed under normal conditions.
    As noted above, dl-Qa, {Oa-cis-hydroxy-3-substituted-6, 6-dimethyl-6,6a, 7,8,10, 10a-hexahydro-9H - dibenzo (b, d () dirane- They are pharmacologically active and useful for obtaining drugs against anxiety and antidepressants, and are prepared from ketals of formula (1). For example, c (-6a-10a-cis-1-hydroxy 3- (1.1) -d-Megylheptyl) - 6,6 - dimethyl-6,6a, 7,8,10,10a-hexahydro-9H - dibenzo (6, d) pyran-9-one can be reacted with aluminum chloride in dichloromethane to full isomerization to the corresponding d / -6a, 10a-TipaHc derivative, 10a-trans-1-hydroxy -3- (1,1dimethylheptyl) -6,6 - dimethyl-6,6a, 7,8,10,10a-gaxacidro-9H - dibenzo (Lb) pyran-9-one The last compound is especially effective in treating people suffering anxiety and / or depression when daily doses are applied, from 0.1 to 100 mg.
    The method is illustrated by the following examples.
    Example 1. a, a-dimethyl-1,4-dioxaspiro (4,5) dec-7-ene-8-methanol; 4- {1-hydroxy-1-methylethyl) -3-cyclohexen-1-one ethylene ketal.
    PacfiBOip 11.0 g of ethylene ketal 4-methoxycarbonyl-3-cyclohexen-1-one in 100 ml of toluene was added dropwise over 30 mi. To a stirred solution of 1100 mmol methyl magnesium bromide in diethyl ether. The reaction mixture was stirred for two hours at 15 ° C and then cooled to 5 ° C and 100 ml of a 1.3 molar aqueous solution of ammonium chloride was added. The organic phase is separated, washed with water, dried and the solvent is removed from it by evaporation under reduced pressure. 6.6 g of 4- (1-hydroxy-1-methylethyl) -3-cyclohexen-1-one ethylene ketal are obtained.
    Analysis: calculated for CnHisOs
    Theor .: C, 66.64; H 9.15; About 24.21.
    Found: C, 66.68; H 9.05; About 24.30.
    NMR / СРС1з (б 1,3) S, 6Н, С / (СНз) 2 б 2,6 (S, Ш, ОН).
    Example 2. a, a, 3,3-tetramethyl-1,5-dioxaspiro (5.5) -unden-5-ene-8-methanol; 2,2-dimethyl-1, 3-prPPandi6l ketal 4- (1-6xi-1metiLethyl) -3-cyclohexen-1-, she.
    The procedure of Example 1 is repeated, but the test temperature is 25 ° C. 80 g of 2,2-dimethyl-1, 3-propanediol ketal, 4- (1-hydroxy-1 methylethyl) -3-cyclograph, exene-1-one are obtained.
    T. pl. 110 ° C.
    Analysis calculated for С14Н240з.
    Calculated: C, 69.96; H 10.07; About 19.27.
    Found: C, 70.17; H 10.11; About 20.07.
    NMR (CDS1) b 1.3 (S, 6H, C (CH3) 2-OH), b 1.0 (2S, 3N each, С-С (СНз) 2-С).
    Example 3. 10a-cis-1-hydroxy-3 (1,1-dimethylheptyl) -6,6-dimethyl-6,6a, 7,8,10,10-hexahydro-9H-dibenzo (s, c) pyran-g-one .
    A solution of 2.30 g of ethylene ketal 4- (1-hydroxy-1-methylethyl-3-cyclohexene-1-bna and 2.12 g of 5 (1,1-dimethyl-g1eptyl) -resorcinol in 50 ml of dichloromethane is stirred and cooled to -10 ° C on ice / acetone bath. To the cooled reaction mixture, 3.6. ml of tin tetrachloride are added dropwise within 5 minutes. In addition to tin tetrachloride, the temperature of the reaction mixture rises from -10 to 0 ° C. After the addition of tin tetrachloride and the reaction mixture the mixture is stirred for another four hours, maintaining the temperature at about -5 ° C. Then the mixture is heated to and continue stirring for another two hours, then washed with water and 1N sodium hydroxide solution and dried. After removing the solvent by evaporation. Under reduced pressure, a solid residue is obtained, which is then Crystallized from 20 ml of m-hexane to give 2.66 g of dl- Qa, 10-cis-1-hydroxy-3- (1,1-dimethylheptyl) -6,6a, 7,8,10,10a - hexahydro-9H-dibenzo (& th) pyran-9-one 89% purity
    T. float 160-162 ° C.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining ketal 4- (1-bksy-1methylethyl) -3-cyclohexene - 1 - it is the General formula (1)
    AT
    g "H
    (one),
    BUT- -fills,
    sns
    where n is an integer equal to 0 or 1; R and RI, independently of one another, are a hydrogen chloride, methyl or ethyl atom, differing in teM, that ketal cyclohexenon carboxylate of the general formula (2)
    x -RI a,
    (2)
    (JOOCH, where R and HI have the above values, are reacted with methyl magnesium bromide in the presence of diethyl ether at a temperature of about -25 ° C. Sources of information taken into account in the examination 1. S. Danishefcky at al., "A Diels -Alder route to cis-fused D-3-octalones, I. Org. 5Chem. 1975, 40. p. 538 (prototype).
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    引用文献:
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    US3906047A|1971-06-14|1975-09-16|Hoffmann La Roche|8-(2,6,6-Trimethyl-4-oxo-2-cyclohexen-1-ylidene-2-methylene-6-methyl-4,6-octadien-3-ol|
    US3929835A|1973-08-29|1975-12-30|Sharps Ass|Alkyl substituted cyclopenta benzopyrans|
    US3968125A|1973-11-05|1976-07-06|Eli Lilly And Company|Dihydroxyhexahydrodibenzo[b,d]pyrans|
    US3928598A|1973-11-05|1975-12-23|Lilly Co Eli|Hexahydro-dibenzo{8 b,d{9 pyran-9-ones as an anti-anxiety drug|
    US4054581A|1976-07-06|1977-10-18|Eli Lilly And Company|Preparation of cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-ones and intermediates therefor|US4133816A|1977-07-12|1979-01-09|Eli Lilly And Company|Preparation of cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-ones and intermediates therefor|
    US4054581A|1976-07-06|1977-10-18|Eli Lilly And Company|Preparation of cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-ones and intermediates therefor|
    US4171315A|1978-03-31|1979-10-16|Eli Lilly And Company|Preparation of cis-hexahydrodibenzopyranones|
    US4395560A|1982-05-24|1983-07-26|Eli Lilly And Company|Preparation of 6a,10a-trans-hexahydrodibenzopyranones|
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    法律状态:
    优先权:
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    US05/702,804|US4054581A|1976-07-06|1976-07-06|Preparation of cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-ones and intermediates therefor|
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