【结 构 式】 |
【分子编号】17907 【品名】2-[(1R)-3,4-dihydro-1H-isochromen-1-yl]ethyl methanesulfonate 【CA登记号】 |
【 分 子 式 】C12H16O4S 【 分 子 量 】256.32264 【元素组成】C 56.23% H 6.29% O 24.97% S 12.51% |
合成路线1
该中间体在本合成路线中的序号:(XII)A synthesis of the R-(+) isomer has also been reported: Reaction of phenethyl alcohol (I) and ethyl 3,3-diethoxypropionate (VI) in the presence of titanium tetrachloride affords the isochromane (VII), which is hydrolyzed to acid (VIII) with NaOH in aqueous ethanol. Resolution of the racemic acid (VIII) is effected by conversion into the diastereomeric salt with R-(+)-a-methylbenzylamine (IX) which, after recrystallization from dichloromethane and ethyl acetate, is liberated by treatment with hydrochloric acid, to yield the R-(-) acid (X). This acid is reduced to alcohol (XI) with borane-dimethyl sulfide in tetrahydrofuran. Treatment of XI with methanesulfonyl chloride, diisopropylethylamine, and a trace of dimethylaminopyridine (DMAP) in tetrahydrofuran affords mesylate (XII), which is subsequently treated with piperazine (V) in ethylene glycol to afford the R-(+) compound, isolated as the methanesulfonate salt.
【1】 TenBrink, R.E.; et al.; (S)-(-)-4-[4-[2-(Isochroman-1-yl)ethyl]-piperazin-1-yl]benzenesulfonamide, a selective dopamine D(4) antagonist. J Med Chem 1996, 39, 13, 2435. |
【2】 Ten Brink, R.E.; Ennis, M.D.; Lin, C.-H.; Lahti, R.A.; Romero, A.G.; Sih, J.C. (Pharmacia Corp.); Heterocyclic cpds. for the treatment of CNS and cardiovascular disorders. EP 0737189; JP 1997507224; US 5877317; WO 9518118 . |
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) | 17897 | Phenethyl alcohol; 2-phenyl-1-ethanol | 60-12-8 | C8H10O | 详情 | 详情 |
(V) | 12143 | 1-(4-Fluorophenyl)piperazine | 2252-63-3 | C10H13FN2 | 详情 | 详情 |
(VI) | 17901 | Ethyl 3,3-diethoxypropanoate | 10601-80-6 | C9H18O4 | 详情 | 详情 |
(VII) | 17902 | ethyl 2-(3,4-dihydro-1H-isochromen-1-yl)acetate | C13H16O3 | 详情 | 详情 | |
(VIII) | 17903 | 2-(3,4-dihydro-1H-isochromen-1-yl)acetic acid | C11H12O3 | 详情 | 详情 | |
(IX) | 20042 | (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine | C8H11N | 详情 | 详情 | |
(X) | 17905 | 2-[(1R)-3,4-dihydro-1H-isochromen-1-yl]acetic acid | C11H12O3 | 详情 | 详情 | |
(XI) | 17906 | 2-[(1R)-3,4-dihydro-1H-isochromen-1-yl]-1-ethanol | C11H14O2 | 详情 | 详情 | |
(XII) | 17907 | 2-[(1R)-3,4-dihydro-1H-isochromen-1-yl]ethyl methanesulfonate | C12H16O4S | 详情 | 详情 |