局部麻醉药罗哌卡因的合成工艺研究  

Study on synthetic process of local anesthetic ropivacaine

作　　者：徐新良 庄程翰 王磊 李华 张兴贤[2] XU Xin-liang;ZHUANG Cheng-han;WANG Lei;LI Hua;ZHANG Xing-xian(Zhejiang Apeloa Pharmaceutical Co.,Ltd.,Dongyang 322118,China;College of Pharmaceutical Sciences,Zhejiang University of Technology,Hangzhou 310032,China)

机构地区：[1]浙江普洛家园药业股份有限公司,浙江东阳322118 [2]浙江工业大学药学院,浙江杭州310032

出　　处：《中国药物化学杂志》2021年第6期422-425,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21877099)。

摘　　要：目的优化罗哌卡因的合成工艺。方法以外消旋体2-哌啶甲酸为起始原料,经手性拆分、酰氯化、酰胺化和N-丙基化得到目标产物罗哌卡因。结果与结论目标产物罗哌卡因结构经核磁共振谱进行确证,总收率为25.6%(以外消旋体2-哌啶甲酸计),纯度为98%(HPLC法),光学纯度为99.7%。该路线步骤简短、操作简便、收率高、反应条件温和、适合工业化生产。Ropivacaine is the(S)-enantiomer of the propyl derivative of N-alkyl pipecoloxylidine.With racemic 2-pipecolic acid as the starting material,ropivacaine was synthesized via chiral resolution,acyl chlorination,amidation and N-propylation.The total yield of ropivacaine was 25.6%(calculated by racemic 2-pipecolic acid)with the purity of 98%(HPLC)and optical purity of 99.7%.The structure of the target compound was confirmed by NMR.This improved process has the advantages of readily available starting materials,mild reaction conditions,easy operations,low cost and high yield.

关 键 词：(S)-2-哌啶甲酸 手性拆分 消旋化 罗哌卡因 合成 

分 类 号：R914[医药卫生—药物化学]