4-二甲氨基巴豆酸的合成工艺研究  

Studies on synthesis of 4-dimethylaminocrotonic acid

作　　者：褚朝森[1,2] 王晓丽[1] 韩世清[3] 胡玉涛[1] 李天雪[1] 

机构地区：[1]江苏联合职业技术学院连云港中医药分院,连云港222007 [2]连云港市药物研发共性技术中心,江苏连云港222007 [3]南京工业大学生物与制药工程学院,江苏南京211800

出　　处：《化学研究与应用》2015年第8期1190-1194,共5页Chemical Research and Application

基　　金：江苏省医学科技发展基金项目(J201417)资助;江苏省"青蓝工程"基金项目(2014)资助

摘　　要：以N,N-二甲基氨基乙醇为原料,经TEMPO氧化、膦酰基乙酸三乙酯活化酯化、水解三步成功合成了4-二甲氨基巴豆酸,总收率81.2%。优选了TEMPO-Na Br-Na Br O3-Na NO2催化体系,确定甲酸乙酯为最佳溶剂,该步收率90.5%;研究了反应条件对酯化反应的影响,确定最佳条件为室温下,反应2h,二氯甲烷为溶剂,N,N-二甲基氨基乙醛、磷酰基乙酸三乙酯、氢化钠三者摩尔比为1∶1.5∶1.5,收率97%;水解反应采用盐酸甲醇溶液代替盐酸水溶液调节p H,选用体积比为乙腈∶丙酮=5∶1的混合溶剂搅拌析晶,收率92.5%。Using N,N-dimethyl amino ethanol as starting material ,4-dimethylaminocrotonic acid with total yield of 81.2% was synthesized via TEMPO oxidation, triethyl phosphonoacetate activated esterification, hydrolysis. With catalytic yield of 90. 5% , TEMPO- NaBr-NaBrO3 -NaNO2 catalytic system was optimized. Ethyl formate was the best solvent in this step. The reaction conditions of es- terification were studied. At room temperature, with dichloromethane as solvent,2 hours,N, N-dimethyl amino acetaldehyde, triethyl phosphonoacetate, sodium hydride mole ratio of 1：1.5：1.5 was the best conditions with 97% yield. Instead of hydrochloric acid aqueous solution,hydrochloric acid methanol solution was used to adjust the pH value in the hydrolysis reaction. At the same time, mixed solvent of aeetonitrile/acetone（5：1, V/V）was Used to generate the crystal with 92. 5% yield.

关 键 词：4-二甲氨基巴豆酸 阿法替尼 TEMPO 膦酰基乙酸三乙酯 

分 类 号：O643.3[理学—物理化学]