氯沙坦的连续流合成工艺研究  

Research on Continuous Flow Synthetic Process of Losartan

作　　者：高锋 戴佳炜 王俊峰 夏春年[1] GAO Feng;DAI Jiawei;WANG Junfeng;XIA Chunnian(College of Pharmacy,Zhejiang University of Technology,Hangzhou 310014;Zhejiang Juxian Pharmaceutical Technology Co.,Ltd.,Taizhou 317016)

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]浙江聚贤医药科技有限公司,浙江台州317016

出　　处：《中国医药工业杂志》2023年第7期1060-1064,共5页Chinese Journal of Pharmaceuticals

摘　　要：在已有文献报道的合成路线基础上,利用微通道反应器技术对氯沙坦(1)的合成进行连续流工艺改造:以2-氰基-4’-甲基联苯(2)和2-丁基-4-氯-5-甲酰基咪唑(3)为起始原料,在微通道反应器内经溴化、N-烷基化及四唑环加成反应制得1,总收率70.3%(以2计),纯度>99.6%。优化后的合成工艺条件温和、操作简便且安全性明显提高,适合工业化生产。Continuous flow process for the synthesis of losartan(1)was realized by microchannel reactor technology based on the synthetic routes reported in the literature.Compound 1 was obtained with an overall yield of 70.3%[based on 2-cyano-4'-methylbiphenyl(2)]via bromination,N-alkylation and tetrazolium cycloaddition reaction using 2 and 2-butyl-4-chloro-1H-imidazole-5-carboxaldehyde(3)as the starting materials.The optimized process bearing mild reaction conditions,simple operation and higher security is suitable for industrial production.

关 键 词：微通道反应器 连续流 氯沙坦 四唑 制药工艺 

分 类 号：TQ460.6[化学工程—制药化工] R972.4[医药卫生—药品]