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【结 构 式】 
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【分子编号】46586 【品名】(1S,4R)-4-(1-hydroxy-1-methylethyl)-1-methyl-2-cyclohexen-1-ol 【CA登记号】 |
【 分 子 式 】C10H18O2 【 分 子 量 】170.25172 【元素组成】C 70.55% H 10.66% O 18.79% |
合成路线1
该中间体在本合成路线中的序号：(II)The aromatic portion of the molecule is generated by the condensation of 1,6-dimethoxyphenol with 1,1-dimethylheptanol in the presence of methanesulfonic acid at 50 C. The crude product is then esterified with diethyl phosphite and triethylamine with cooling to yield the diethyl phosphate derivative. Reduction with lithium in liquid ammonia produces 1-(1',1'-dimethylheptyl)-3,5-hydroxybenzene (I) which is processed crude to the next step. This involves the condensation of the p-menthenediol (II) with the dimethylheptyl resorcinol (I) catalyzed by p-toluenesulfonic acid to give the dimethylheptyl analog of DELTA8-THC (III). Following acetylation of the phenolic group, the allylic methyl group is oxidized to the aldehyde (IV) using selenium dioxide. Further oxidation to the carboxylic acid is accomplished by the use of sodium chlorite. Finally, ajulemic acid is obtained by removal of the acetyl group with sodium carbonate in aqueous methanol.
| 【1】 Burnstein, S.; Ajulemic Acid. Drugs Fut 2001, 26, 4, 342. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 20233 | 5-(1,1-dimethylheptyl)-1,3-benzenediol | C15H24O2 | 详情 | 详情 | |
| (II) | 46586 | (1S,4R)-4-(1-hydroxy-1-methylethyl)-1-methyl-2-cyclohexen-1-ol | C10H18O2 | 详情 | 详情 | |
| (III) | 46587 | (6aR,10aR)-3-(1,1-dimethylheptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-yl acetate | C27H40O3 | 详情 | 详情 | |
| (IV) | 46588 | (6aR,10aR)-3-(1,1-dimethylheptyl)-9-formyl-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-yl acetate | C27H38O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Grignard reaction between 3,5-dimethyoxybenzonitrile (I) and 4-bromophenoxybutane (II) in the presence of Mg turnings in THF, followed by hydrolysis with HCl, affords ketone (III), which is then treated with TiCl4 in dichloromethane and dimethyl zinc (Me2Zn) in toluene to provide dimethylpentane derivative (IV). Bromination of (IV) is then accomplished by first azeotroping with benzene followed by treatment with BBr3 in dichloromethane, affording bromo derivative (V). Condensation of resorcinol derivative (V) with p-menth-2-ene-1,8-diol (VI) in refluxing benzene in the presence of p-toluensulfonic acid furnishes compound (VII), whose bromo group is substituted by a cyano group by treatment with NaCN in DMSO giving derivative (VIII). Finally, condensation of (VIII) with 4-morpholinobutyric acid hydrochloride (IX) by means of DCC in dichloromethane provides the target product.
| 【1】 Razdan, R.K.; Martin, B.R. (Virginia Commonwealth University); Water soluble derivs. of cannabinoids. US 5847128 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 47231 | 3,5-dimethoxybenzonitrile | 19179-31-8 | C9H9NO2 | 详情 | 详情 |
| (II) | 47232 | 4-bromobutyl phenyl ether; 1-(4-bromobutoxy)benzene | 1200-03-9 | C10H13BrO | 详情 | 详情 |
| (III) | 47233 | 1-(3,5-dimethoxyphenyl)-5-phenoxy-1-pentanone | C19H22O4 | 详情 | 详情 | |
| (IV) | 47234 | 1-(1,1-dimethyl-5-phenoxypentyl)-3,5-dimethoxybenzene; 5-(3,5-dimethoxyphenyl)-5-methylhexyl phenyl ether | C21H28O3 | 详情 | 详情 | |
| (V) | 47235 | 5-(5-bromo-1,1-dimethylpentyl)-1,3-benzenediol | C13H19BrO2 | 详情 | 详情 | |
| (VI) | 46586 | (1S,4R)-4-(1-hydroxy-1-methylethyl)-1-methyl-2-cyclohexen-1-ol | C10H18O2 | 详情 | 详情 | |
| (VII) | 47236 | (6aR,10aR)-3-(5-bromo-1,1-dimethylpentyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol | C23H33BrO2 | 详情 | 详情 | |
| (VIII) | 47237 | 6-[(6aR,10aR)-1-hydroxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-3-yl]-6-methylheptanenitrile | C24H33NO2 | 详情 | 详情 | |
| (IX) | 47238 | 4-(3-carboxypropyl)morpholin-4-ium chloride | C8H16ClNO3 | 详情 | 详情 |