罗氟司特的合成研究  

Study on Process of Synthesizing Roflumilast

作　　者：刘昭文[1] 杨凯[1] 郭小华[1] 曾发挥[1] LIU Zhao-Wen;YANG Kai;GUO Xiao-Hua;ZENG Fa-Hui(College of Pharmacy Gannan Medical University,Ganzhou 341000,China)

机构地区：[1]江西省赣南医学院药学院,赣州341000

出　　处：《海峡药学》2018年第10期87-88,共2页Strait Pharmaceutical Journal

基　　金：赣南医学院校级课题(No.YB201413)

摘　　要：目的改进罗氟司特的合成工艺。方法以4-二氟甲氧基-3-羟基苯甲酸乙酯为起始原料,经O-烷基化、水解、氯化、酰胺化反应重结晶得到目标物罗氟司特。结果罗氟司特合成总收率为52. 8%,纯度99. 6%,所得产品经质谱(MS)、核磁共振氢谱(1H-NMR)和红外光谱(IR)确证。结论改进后的工艺过程简单,反应条件温和,生产安全,环境友好,产品收率高,有利于工业化大生产。OBJECTIVE To improve the synthesis process of roflumilast.METHODS Roflumilast was synthesized from 4-difluoromethoxy-3-hydroxybenzoic acid ethyl ester via O-alkylation,hydrolysis and N-acylation.RESULTS The total yield was 52.8%,and the purity was 99.6%.Thestructure of target compound was confirmed by MS,1H-NMR and IR. CONCLUSION This process had the advantages of simple operation,mild reaction conditions,low dangerness,environment friendly,good yield,and suitable for industrial production.

关 键 词：4-二氟甲氧基-3-羟基苯甲酸乙酯 O-烷基化 合成 罗氟司特 

分 类 号：R917[医药卫生—药物分析学]