瑞格列奈的合成

Synthesis of Repaglinide

研究了适合瑞格列奈产业化的合成工艺。以4-羧甲基-2-乙氧基苯甲酸酯为原料,与特戊酰氯反应生成活性中间体,再与(S)-3-甲基-1-[2-(1-哌啶基)苯基]丁胺一锅法合成了2-乙氧基-4-{2-{[(1S)-3-甲基-1-[2-(1-哌啶基)苯基]丁基]氨基}-2-氧代乙基}苯甲酸乙酯,经水解合成目标产物瑞格列奈。结果表明:用新方法合成的瑞格列奈纯度高,收率高达63%,该法反应条件温和,操作简单,环境友好,有工业化生产前景。

A new synthesis method of repaglinide industrialization was studied. 4-Carboxymethy1-2- ethoxy benzoic acid ester reacted with pivaloyl chloride toform active intermediate, then by one pot method,2-oxethyl-4-{2-{[（1S） - 3- methyl -1-[2- （1- piperidyl） phenyl1 butyl]amino}-2- oxygen generation ethyl} ethyl benzoate was synthe- sized from （S） -3- methyl -1-[2-（1-piperidyl） penyl] butylamine, the target compound was synthesized by the hydrolysis of repaglinide. The results showed that the new synthesis method of repaglinide had higher purity, higher yield which was up to 63%,a mild reaction condition,convenient operation,friendly environment,and was suitable to large scale manufacturing.