奈韦拉平的制备工艺  

Research on the Preparation Process of Nevirapine

作　　者：马良秀 左慧 徐峰[2] MA Liang-xiu;ZUO Hui;XU Feng(Zhejiang Lepu Pharmaceutical Co.,Ltd.,Taizhou 318000,China;Chemical Pharmaceutical Research Institute,Taizhou Vocational and Technical College,Taizhou 318000,China)

机构地区：[1]浙江乐普药业股份有限公司,浙江台州318000 [2]台州职业技术学院化学制药研究所,浙江台州318000

出　　处：《合成化学》2021年第3期236-240,共5页Chinese Journal of Synthetic Chemistry

基　　金：浙江省基础公益研究项目(LGF19B020001)。

摘　　要：以2-氯烟酸和2-氯-3-氨基-4-甲基吡啶为起始原料合成中间体Ⅰ;然后通过氨化和环化反应,在微通道反应器中连续化合成奈韦拉平中间体Ⅱ和奈韦拉平;在合成中间体Ⅱ的反应中考察反应温度、反应物料摩尔比和气体流速对反应的影响;合成奈韦拉平的反应中重点考察反应温度对反应的影响。结果表明:合成中间体Ⅱ的最佳工艺条件为反应温度为90℃,物料摩尔比n(中间体Ⅰ)/n(环丙胺)=1/1.2,氮气流速为25 mL/min为最佳;合成奈韦拉平的最佳工艺条件是反应温度为110℃。在最佳工艺条件下,中间体Ⅱ的转化达到率为99.5%以上,选择性为99%以上。IntermediateⅠof Nevirapine was prepared from 2-chloronicotinic acid and 2-chloro-3-amino-4-methyl pyridine as the start materials.IntermediatesⅡand Nevirapine were continuously synthesized from IntermediateⅠvia amination and cyclization reaction in a microreactor,respectively.The effect of reaction temperature,reaction material molar ratio and gas flow rate on the preparation of intermediatesⅡwere investigated,and in the process of synthesis of Nevirapine was focused on reaction temperature.The results show that the best process conditions for preparation of intermediateⅡis the reaction temperature:90℃,reaction material molar ratio:n(IntermediateⅠ)/n(Cyclopropylamine)=1/1.2,gas flow rate:25 mL/min.And the best reaction temperature for preparation of Nevirapine is 110℃.Under the best process conditions,the conversion rate of intermediateⅡis more than 99.5%,and the selectivity is more than 99%.

关 键 词：连续催化反应 奈韦拉平 负载型固体碱 负载型固体超强碱 合成 

分 类 号：O621.25[理学—有机化学] R914.5[理学—化学]