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.
作者
乔玉辉
孙英杰
邹胜
黄冲
朱槿
黄晴菲
王启卫
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)
出处
《合成化学》
CAS
北大核心
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
关键词
吡啶
兰索拉唑
中间体合成
工艺优化
放大实验
pyridine
lansoprazole
intermediate synthesis
process improvement
scale-up experiment
作者简介
乔玉辉(1992-),男,汉族,河北邯郸人,硕士研究生,主要从事有机合成的研究。E-mail:1165200098@qq.com;通信联系人:黄晴菲,副研究员,硕士生导师,E-mail:qfhuang@cioc.ac.cn。
