外消旋邻氯扁桃酸的非对映体拆分。

Diastereomeric resolution of racemic o-chloromandelic acid.

机构信息

School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, People's Republic of China.

出版信息

Chirality. 2012 Dec;24(12):1013-7. doi: 10.1002/chir.22089. Epub 2012 Jun 22.

DOI:10.1002/chir.22089

PMID:22730179

Abstract

The separation of rac-o-chloromandelic acid 1 with enantiopure aryloxypropylamine via diastereomeric salt formation was investigated. (R)-o-chloromandelic acid (R)-1, a key intermediate for the antithrombotic agent clopidogrel, was obtained in 65% yield and 98% ee by Dutch resolution of rac-1 with (S)-2-hydroxyl-3-(p-chlorophenoxy) propylamine (S)-5 as resolving agent and (S)-2-hydroxyl-3-(o-nitrophenoxy) propylamine (S)-4 as nucleation inhibitor.

摘要

通过非对映立体盐形成对 rac-o-氯苯甘氨酸 1 进行拆分，研究了 rac-o-氯苯甘氨酸 1 的对映选择性拆分。（R）-o-氯苯甘氨酸（R）-1 是抗血栓药物氯吡格雷的关键中间体，通过 rac-1 与（S）-2-羟基-3-（对氯苯氧基）丙胺（S）-5 作为拆分剂和（S）-2-羟基-3-（邻硝基苯氧基）丙胺（S）-4 作为成核抑制剂的荷兰拆分，以 65%的收率和 98%的对映体过量值（ee）得到。