2,3-二甲基-4-(2,2,2-三氟乙氧基)吡啶-1-氧化物的合成  

Synthesis of 2,3-Dimethyl-4-(2,2,2-trifluoroethoxy) pyridine-1-oxide

作　　者：乔玉辉 孙英杰 邹胜[1] 黄冲 朱槿[1] 黄晴菲[1] 王启卫[1] QIAO Yu-hui;SUN Ying-jie;ZOU Sheng;HUANG Chong;ZHU Jin;HUANG Qing-fei;WANG Qi-wei(Chengdu Institute of Organic Chemistry,Chinese Academy of Sciences,Chengdu 610041,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院成都有机化学研究所,四川成都610041 [2]中国科学院大学,北京100049

出　　处：《合成化学》2019年第12期978-981,共4页Chinese Journal of Synthetic Chemistry

基　　金：中科院“西部之光”人才培养计划

摘　　要：以2,3-二甲基-4-硝基吡啶-1-氧化物为原料,合成兰索拉唑中间体2,3-二甲基-4-(2,2,2,-三氟乙氧基)吡啶-1-氧化物(2),其结构经1 H NMR确证。研究了溶剂、催化剂、碱和反应时间等因素对2收率的影响。结果表明:在最优反应条件(乙腈作溶剂,三氟乙醇2.0 eq.,碳酸钾2.5 eq.,在1 mol%TBAB水溶液中反应10 h)下,2收率超过85%。将实验规模放大到100 g级,工艺稳定。A key intermediate of lansoprazole,2,3-dimethyl-4-(2,2,2-trifluroethoxy)pyridine-1-oxide(2),was synthesized using 2,3-dimethyl-4-nitropyridine-1-oxide as starting material.The structure was confirmed by 1 H NMR.The effect of solvent,catalyst,base,reaction time and material ratio on the reaction were studied.The results showed that in the presence of 1 mol%TBAB aqueous solution,using acetonitrile as solvent with addition of 2 eq.trifluoroethanol,2.5 eq.potassium carbonate,compound 2 can be obtained by over 85%yield when reacting for 10 h.The process is still stable when the amount of raw material increased to 100 g.

关 键 词：吡啶 兰索拉唑 中间体合成 工艺优化 放大实验 

分 类 号：O626[理学—有机化学] R914.5[理学—化学]