二氟尼柳的新合成工艺  

A Novel Synthetic Process of Diflunisal

作　　者：刘秋连 

机构地区：[1]湘潭食品药品检验所,湖南湘潭411100

出　　处：《中国医药工业杂志》2018年第2期172-174,共3页Chinese Journal of Pharmaceuticals

摘　　要：本研究设计了一条新路线合成二氟尼柳(1)。2-氯苯腈(2)经N-溴代琥珀酰亚胺溴化得2-氯-5-溴苯腈(3),3在六水合氯化镍/三苯基膦在线生成的双三苯基膦氯化镍催化下,和2,4-二氟苯硼酸(4)偶联得4-氯-2',4'-二氟-(1,1'-联苯)-3-甲腈(5),5再经氢氧化钠水解得化合物1,总收率63.1%(以2计)。其中,由化合物3和4制备5的方法未见文献报道。本工艺反应条件温和,后处理简便,更适合放大生产。A novel synthetic process of diflunisal （1） was reported. 2-Chloro-5-bromobenzonitrile （3） was prepared via bromination by N-bromosuccinimide from 2-chlorobenzonitrile （2）. Then 3 coupled with （2,4-difluorophenyl）boronic acid （4） catalyzed by bis（triphenylphosphine）dichloronickel which formed by nickel chloride hexahydrate and triphenylphosphine to afford 4-chloro-2＇,4＇-difluoro-（1,1＇-biphenyl）-3-carbonitrile （5）. Finally, compound 5 was subjected to hydrolysis in autoclave to prepare 1 with an overall yield of 63.1%（based on 2）. This new process has some advantages, such as mild reaction conditions and simple operation, which are more suitable for commercial production.

关 键 词：二氟尼柳 非甾体抗炎药 2 4-二氟苯硼酸 镍催化偶联 合成 

分 类 号：R971.1[医药卫生—药品] R914.5[医药卫生—药学]