手性中间体(R)-4-氰基-3-羟基丁酸乙酯制备工艺改进  

Improvement of Preparation Process Chiral Intermediate Ethyl(R)-4-Cyano-3-hydroxybutyrate

作　　者：徐斌 柴多武 洪治 Xu Bin;Chai Duowu;Hong Zhi(Yekelai Taizhou Pharmaceutical Company,Linhai 317016,China)

机构地区：[1]弈柯莱(台州)药业有限公司,台州临海317016

出　　处：《广东化工》2024年第16期39-41,共3页Guangdong Chemical Industry

摘　　要：开发了一种绿色环保的阿托伐他汀手性中间体(R)-4-氰基-3-羟基丁酸乙酯的制备工艺。该工艺采用双固定化酶法合成,以4-氯乙酰乙酯为起始原料,先用ADH酶还原生成(S)-(-)-4-氯-3-羟基丁酸乙酯,然后在脱卤酶的催化下与氰化钠反应制得(R)-4-氰基-3-羟基丁酸乙酯。该制备工艺简单反应条件温和,原子经济性高,其总收率可达到85%以上。A green and environmentally friendly chiral intermediate of atorvastatin(R)-4-cyano-3-hydroxybutyrate was developed.Double immobilized enzyme is used in this process,4-chloroacetyl ethyl ester as the starting material was first reduced by ADH enzyme to get(S)-(-)-chloro-3-hydroxy-butyrate ethyl ester,and then(R)-4-cyano-3-hydroxy-butyrate ethyl ester was prepared by reaction with sodium hydrocyanic under the catalysis of dehalogenase enzyme.The preparation process is simple,the reaction conditions are mild,the atomic economy is high,and the total yield can reach more than 85%.

关 键 词：阿托伐他汀 手性中间体 (R)-4-氰基-3-羟基丁酸乙酯 双固定化酶法合成 脱卤酶 

分 类 号：TQ46[化学工程—制药化工]