依法韦仑中间体的合成工艺优化  

Optimization of Synthesis of Efavirenz Intermediate

作　　者：吴高鑫 郑云峰 罗海荣 Wu Gaoxin 1,Zheng Yunfeng 1,Luo Hairong 2(1. ZheJiang Hisunpharm Co.,Ltd.,Taizhou 318000,China;2.School of Material and Chemical Engineering,Tongren University,Tongren 554300,Chin)

机构地区：[1]浙江海正药业股份有限公司,浙江台州318000 [2]铜仁学院材料与化学工程学院,贵州铜仁554300

出　　处：《山东化工》2018年第14期18-19,共2页Shandong Chemical Industry

摘　　要：以环丙基甲醛为原料,与三氯乙酸、醋酐、锌粉反应制得1-(2,2-二氯乙烯基)环丙烷,继而在碳酸铯作用下反应得到依法韦仑中间体环丙基乙炔,并对消除反应进行了优化:用碳酸铯代替甲基锂,考察了碳酸铯的用量、反应温度对反应的影响,最终确定了最佳反应条件:碳酸铯1.2 eqiv,甲苯/PEG-400体系,110℃反应8 h,总收率79%。产物结构经1H NMR和13C NMR确证。Cycloprotylene,an intermediate of Efavirenz,was synthesized from cyclopropanecarb oxaldehyde with trichloroacetic acid,acetic anhydride and zinc to give 1-（ 2,2-dichlorovinyl） cyclopropane,followed elimination by caesium carbonate. The step of elimination reaction was optimized： caesium carbonate was used in place of methyllithium to form 1 and the effects of mount and temperature on the reaction were explored. The optimum reation conditions were determined： caesium carbonate1. 2 eqiv. in toluene/PEG-400,at 110℃ for 8 h,and the overall yield is 79%. The structure was confirmed by1 H NMR and13 C NMR.

关 键 词：环丙基乙炔 依法韦仑 中间体 合成 

分 类 号：TQ465[化学工程—制药化工]