奥美拉唑的合成  

Synthesis of Omeprazole

作　　者：万欢[1] 方峰[1] 段梅莉[1] 许煦[2] 冀亚飞[1] 

机构地区：[1]华东理工大学药学院,上海200237 [2]华东理工大学化工学院,上海200237

出　　处：《应用化学》2009年第2期178-181,共4页Chinese Journal of Applied Chemistry

基　　金：华东理工大学科研基金资助项目(YJ0142114)

摘　　要：由2,3,5-三甲基吡啶经氧化、硝化一锅煮方法制得2,3,5-三甲基-4-硝基吡啶-N-氧化物。该产物与三氯异氰尿酸直接进行氯化反应得到关键中间体2-氯甲基-3,5-二甲基-4-硝基吡啶-N-氧化物,在过量的甲醇钠存在下与2-巯基-5-甲氧基苯并咪唑同时进行缩合和甲氧基化反应制得5-甲氧基-2-[(4-甲氧基-3,5-二甲基吡啶-N-氧化物)-甲硫基]-1H-苯并咪唑。产物再经三氯化磷还原和高硼酸钠氧化最终制得奥美拉唑,总收率为48.7%。中间体和奥美拉唑的结构经1HNMR、MS测试技术确证。A new synthetic procedure was designed for the preparation of omeprazole. A one-pot method was performed for the oxidation of 2,3,5-trimethylpyridine and the nitration of 2,3,5-dimethylpyridine-N-oxide to get 2,3,5-dimethyl-4-nitropyridine-N-oxide, which was directly chlorinated with trichloroisocyanuric acid to provide the key intermediate 2-chloromethyl-3,5-dimethyl-4-nitropyridine-N-oxide. The chloromethylnitropyri- dine was treated with 2-mercapto-5-methoxybenzimidazole in the presence of excess sodium methoxide to simultaneously carry out the condensation and the methoxylation to give 5-methoxy-2-[ （4-methoxy-3,5-dimethylpyridinyl-N-oxide）-methyhhio]-lH-benzimidazole, from which omeprazole was finally obtained via the deoxidization with phosphorus trichloride and the oxidation with sodium perborate in an ov.erall yield of 48.7%. The structures of the intermediates and omeprazole were confirmed by ^1H NMR and MS.

关 键 词：奥美拉唑 质子泵抑制剂 三氯异氰尿酸 四水合高硼酸钠 

分 类 号：O626.2[理学—有机化学]