R-和S-兰索拉唑的合成工艺研究  

Research on Synthesis Process of R-and S-Lansoprazole

作　　者：葛执信[1] 张灿[1] 

机构地区：[1]中国药科大学新药研究中心,江苏南京211198

出　　处：《药学进展》2012年第7期325-327,共3页Progress in Pharmaceutical Sciences

摘　　要：目的:对R-和S-兰索拉唑的不对称氧化合成反应进行研究。方法:以2-氯甲基-3-甲基-4-(2,2,2-三氟乙氧基)吡啶盐酸盐和2-巯基苯并咪唑为原料,经亲核取代和碱化得中间体2-[[[3-甲基-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲基]硫基]-1H-苯并咪唑,后者经氢过氧化异丙基苯不对称氧化,生成R-和S-兰索拉唑。结果:所制R-和S-兰索拉唑获得结构确证,其总收率均达到65.5%。结论:该法原料利用率高,工艺简单,适用于工业化生产。Objective：To study the synthesis of R-and S-lansoprazole by asymmetric oxidation.Methods：The intermediate 2-[3-methyl-4-（2,2,2-trifluoroethoxy）-2-pyridinyl]methylthio-1H-benzimi-dazole was synthesized from 2-chloromethyl-3-methyl-4-（2,2,2-trifluoroethoxy） pyridine hydrochloride and 2-mercaptobenzimidazole by nucleophilic substitution and alkalization.The R-and S-lansoprazole was obtained from the above intermediate by asymmetric oxidation.Results：The obtained R-and S-lansoprazole was confirmed by IR,1H-NMR and MS.The overall yield of the products both reached 65.5%.Conclusion：The raw material can be highly utilized by this method.The process is also simple and suitable for industrial production.

关 键 词：兰索拉唑 不对称氧化 单一对映体 

分 类 号：R914[医药卫生—药物化学]