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【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information