引用本文:
宋光伟, 朱锦桃, 姚国新, 陈刚. (S)-美托洛尔的不对称合成[J]. 应用化学,
2010, 27(11): 1286-1290.
doi:
10.3724/SP.J.1095.2010.90880
Citation: SONG Guang-Wei, ZHU Jin-Tao, YAO Guo-Xin, CHEN Gang. Asymmetric Synthesis of (S)-Metoprolol[J]. Chinese Journal of Applied Chemistry, 2010, 27(11): 1286-1290. doi: 10.3724/SP.J.1095.2010.90880
Citation: SONG Guang-Wei, ZHU Jin-Tao, YAO Guo-Xin, CHEN Gang. Asymmetric Synthesis of (S)-Metoprolol[J]. Chinese Journal of Applied Chemistry, 2010, 27(11): 1286-1290. doi: 10.3724/SP.J.1095.2010.90880
(S)-美托洛尔的不对称合成
摘要:
用自制的(S,S)-SalenCo(Ⅲ)OAc催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯的(S)-3-氯-1,2-丙二醇和较高光学纯的(R)-环氧氯丙烷。以(S)-3-氯-1,2-丙二醇为手性原料和4-(2-甲氧基乙基)苯酚缩合,再与氯化亚砜反应得环状亚硫酸酯,最后和异丙胺反应得(S)-美托洛尔,光学纯度大于99%。另外以(R)-环氧氯丙烷为手性原料和4-(2-甲氧基乙基)苯酚反应,再与异丙胺作用得到(S)-美托洛尔,光学纯度大于92%。(S)-美托洛尔的总收率为53.9%,结构经IR、1HNMR、13CNMR和MS测试技术确证。该路线原料利用率高,拆分后的2种产物均能用于目标化合物的合成。
English
Asymmetric Synthesis of (S)-Metoprolol
Abstract:
Enantioenriched(S)-3-chloro-1,2-propanediol and(R)-epichlorohydrin were obtained from the kinetic hydrolysis resolution of racemic epichlorohydrin by(S,S)-salen Co(Ⅲ) OAc.(S)-Metoprolol with optical purity higher than 99% could be prepared via the reaction of 4-(2-methoxyethyl) phenol with(S)-3chloro-1,2-propanediol followed by an amination reaction using isopropyl amine.When (R)-epichlorohydrin was used as the chiral precursor,(S)-metoprolol could be also prepared but with less optical purity(>92%). The overall yield of(S)-metoprolol was 53.9%.The structure of the product was determined by IR,1H NMR,13C NMR and MS.This procedure is effective,simple and has a high utilization rate of raw material.The optical purity and yield of the product are satisfactory.The process is promising for scaling-up industrial potential applications.
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