氟雷拉纳的合成工艺研究  

Study on the Synthesis Process of Fluralaner

作　　者：马居良 杨斐 MA Juliang;YANG Fei(Shandong Jiulong Hisince Pharmaceutical Co.,Ltd.,Dezhou 251100,China;School of Pharmaceutical Sciences,Shandong UniversitiyJinan 250012,China)

机构地区：[1]山东久隆恒信药业有限公司,山东德州251110 [2]山东大学药学院,山东济南250012

出　　处：《山东化工》2025年第3期77-80,84,共5页Shandong Chemical Industry

摘　　要：主要研究了以4-溴-2-甲基-苯甲酸为起始物料与正丁基乙烯基醚发生取代反应生成4-乙酰基-2-甲基苯甲酸,依次与2-氨基-N-(2,2,2-三氟乙基)乙酰胺发生缩合反应,与3,5-二氯苯甲醛发生加成反应,与叔丁基亚硝酸酯发生异环化反应,与(三氟甲基)三甲基硅烷发生取代反应,最后进行还原反应生成氟雷拉纳。通过控制各步反应中催化剂的种类及用量,使每步反应都有较高的收率,最终以较高产率得到氟雷拉纳,产品纯度99%以上。This article mainly studies the substitution reaction of 4-bromo-2-methylbenzoic acid with n-butyl vinyl ether to produce 4-acetyl-2-methylbenzoic acid,followed by condensation reaction with 2-amino-N-(2,2,2-trifluoroethyl)acetamide,addition reaction with 3,5-dichlorobenzaldehyde,heterocyclization reaction with tert butyl nitrite,substitution reaction with(trifluoromethyl)trimethylsilane,and finally reduction reaction to produce Fluralaner.By controlling the type and amount of catalyst in each step of the reaction,a high yield is achieved in each step,resulting in the final production of Fluralaner with a purity of over 99%.

关 键 词：4-溴-2-甲基-苯甲酸 氟雷拉纳 催化剂 

分 类 号：TQ453[化学工程—农药化工]