第 50 卷第 6 期 Vol. 50 No. 6 2020 年 12 月 Dec 2020

所属栏目：医药及中间体 （2S）-N-二苯甲基-2-吡咯甲酰胺的合成工艺优化

邓护军，王军绪，付国兵，张 宁，梁春梅 （西安万隆制药股份有限公司，陕西 西安 710119）

摘　要：以廉价易得的二苯甲醇为起始物料，依次经氯化、氨解、酰胺化3步反应合成了（2S）-N-二苯甲基-2-吡咯甲酰胺。优化的工艺条件为：氯化反应以氯化亚砜作氯源；氨解反应纯化溶剂n（乙酸乙酯）∶n（异丙醇）=1∶3、打浆温度10~20 ℃；酰胺化反应时间3 h。优化后的反应总收率65.3%，产品纯度98.5%。合成路线简便，工艺稳定。

关键词：（2S）-N-二苯甲基-2-吡咯甲酰胺；二苯氯甲烷；工艺优化

中图分类号：R914　　文献标识码：A　　文章编号：1009-9212（2020）06-0041-04

The Optimization of Synthesis Process of (2S)-N-Diphenylmethyl-2-pyrrolidinecarboxamide

DENG Hu-jun, WANG Jun-xu, FU Guo-bing, ZHANG Ning, LIANG Chun-mei (Xi'an WanLong Pharmaceutical Co., Ltd., Xi'an 710119, China)

Abstract：The pharmaceutical intermediate, (2S)-N-diphenylmethyl-2-pyrrolidinecarboxamide, was synthesized through a series of reactions including chlorination, ammonolysis, and amidation with using commercialized diphenylmethanol as the starting material. The main factors influencing the reactions were investigated. The experimental results showed that: using thionyl chloride as chlorine source, the solvent molar ratio of ethyl acetate to isopropyl alcohol is 1∶3, and the purification temperature is 10~20 ℃, the amidation time is 3 h. The overall yield amounts to 65.3% and the purity reached 98.5%. The route has mild reaction conditions and simple operation, and is suitable for industrial scale production．

Key words：(2S)-N-diphenylmethyl 2-pyrrolidinecarboxamide; chlorodiphenylmethane; process optimization

基金项目：陕西省自然科学基础研究计划（面上）（2018JM7046）。

作者简介：邓护军（1969—），男，陕西西安人，工程师，主要从事药物合成与研发。

收稿日期：2020-11-09