度鲁特韦关键中间体的合成及分子蒸馏提纯工艺  

Synthesis of A Key Intermediate for Dolutegravir and Its Refining by Molecular Distillation

作　　者：刘玮 樊振 李宏卫 马珍珍 毛龙飞 姜玉钦 LIU Wei;FAN Zhen;LI Hong-wei;MA Zhen-zhen;MAO Long-fei;JIANG Yu-qin(China Pharmaceutical Health Industry Co.LTD.,Beijing 100061,China;Topfond Pharmaceutical Co.Ltd.,Zhumadian 463000,China;School of Chemistry and Chemical Engineering,Henan Engineering Research Center of Chiral Hydroxyl Pharmaceutical,Henan Normal University,Xinxiang 453007,China)

机构地区：[1]中国医药健康产业股份有限公司,北京100061 [2]天方药业有限公司,河南驻马店463000 [3]河南师范大学化学化工学院河南省手性醇类药物工程技术研究中心,河南新乡453007

出　　处：《合成化学》2018年第9期703-706,710,共5页Chinese Journal of Synthetic Chemistry

基　　金：2015年度河南省重点科技攻关项目(152102210285);河南省产学研项目(142107000081)

摘　　要：4-甲氧基乙酰乙酸甲酯是合成抗HIV新药度鲁特韦的关键中间体。本文以4-氯乙酰乙酸甲酯与甲醇为起始原料,氢化钠和甲醇钾作为混合碱,合成4-甲氧基乙酰乙酸甲酯,通过分子蒸馏法对其进行提纯获得纯品,总收率88%,纯度99. 7%,其结构经~1H NMR和^(13)C NMR确证。并对分子蒸馏工艺条件进行了优化。4-Methoxyacetoacrtic acid methyl ester was a keyintermediate for synthesis of dolutegravir. This study reported a new protocol for the synthesis and refining of 4-methoxyacetoacrtic acid methyl ester via molecular distillation. The impurities can be reduced using NaH and CH 3 OK as catalyst and using molecular distillation for purification. The product was prepared in total yield of 88% and the purity could be reached to 99.7% under the optimized condition. The structure was confirmed by 1 H NMR and 13 C NMR. The conditions for molecular distillation were optimized.

关 键 词：4-甲氧基乙酰乙酸甲酯 度鲁特韦 氢化钠 甲醇钾 合成 分子蒸馏 

分 类 号：TQ463[化学工程—制药化工]