非布司他合成工艺研究  

Study on febuxostat synthesis process

作　　者：马宁宁 刘晓莲 杨藏军 韩啸 葛娜 代景茹 Ma Ningning;Liu Xiaolian;Yang Cangjun;Han Xiao;Ge Na;Dai Jingru(Hebei Jiheng Pharmaceutical Corporation Ltd.,Hengshui 053400,China)

机构地区：[1]河北冀衡药业股份有限公司,河北衡水053400

出　　处：《煤炭与化工》2022年第10期125-128,共4页Coal and Chemical Industry

摘　　要：提供了一种非布司他合成方法,以2-(3-醛基-4-羟基苯基)-4-甲基-5-甲酸乙酯噻唑为起始原料,经过异丁基化反应、氰基化反应和水解反应合成非布司他。最佳工艺条件为:n[2-(3-醛基-4-羟基苯基)-4-甲基-5-甲酸乙酯噻唑(中间体3)]∶n(1-溴代异丁烷)∶n(K_(2)CO_(3))=1∶2.5∶2,90℃,反应4 h,合成中间体4,n(中间体4)∶n(盐酸羟胺)=1∶1.85,110℃,反应4 h得中间体5,最后中间体5在碱性环境中60℃水解4 h得非布司他产品。非布司他总收率为68%,纯度99.72%,单杂0.09%,总杂0.28%。A nonbuxostat synthesis method was provided with 2-(3-aldehyde-4-hydroxyphenyl)-4-methyl-5-ethyl formate thiazole as the starting material,after an isobutylation reaction,cyanogenylation reaction and hydrolysis reaction.The optimal process conditions are as follows:n[2-(3-aldehyde-4-hydroxyphenyl)-4-methyl-5-ethyl methyl thiazole(intermediate 3)]∶n(1-bromide isobutane)∶n(K_(2)CO_(3))=1∶2.5∶2,90℃,reaction 4 h,synthesis 4,synthetic intermediate 4,n(intermediate 4)∶n(hydroxylamin hydrochloride)=1∶1.85,110℃,reaction 4 h intermediate 5,finally 60℃hydrolyzed for 4h in alkaline environment.Fibuxostat yield was 68%overall,with 99.72%pure,0.09%miscellaneous alone,and 0.28%miscellaneous overall.

关 键 词：非布司他 异丁基化反应 氰化反应 水解反应 

分 类 号：TQ464.5[化学工程—制药化工]