An improved preparing process for rivastigmine
10.11665/j.issn.1000-5048.20150406
- VernacularTitle:一种改进的卡巴拉汀制备工艺
- Author:
Jiaquan WU
1
;
Ping ZHOU
;
Yang LIU
;
Chuanming JIE
;
Huanyan CAO
;
Tao PENG
;
Xiaohong LI
;
Haijun ZHANG
Author Information
1. 科里生物医药中国(江阴)研究院
- Publication Type:Journal Article
- Keywords:
rivastigmine;
asymmetric synthesis;
CBS reduction;
process improvement
- From:
Journal of China Pharmaceutical University
2015;46(4):421-425
- CountryChina
- Language:Chinese
-
Abstract:
An improved manufacturing process for rivastigmine(1)was developed by performing the condensation reaction of m-hydroxyacetophenone(4)with N-ethyl-N-methyl carbamoyl chloride, then Corey-Bakshi-Shibata(CBS)chiral reduction to(R)-3-(1-hydroxyethyl)phenyl ethyl(methyl)carbamate(2)and then mesylation with methanesulfonyl chloride and nucleophilic substitution with dimethylamine, respectively. To be successful, a crucial reductive process in the conversion of ketone(3)to chiralalcohol(2)had to be correctly understood and optimized via orthogonal experiment. The whole improved process was convenient for operation and purification, with completion of the synthesis of rivastigmine and an overall yield of 88%.
