西他列汀关键中间体的合成研究  

Research on the Synthesis of Key Intermediate of Sitagliptin

作　　者：陈云华[1,2] 谭建德 周魏魏 缪炳林 徐龙 周丽萍 CHEN Yun-hua;TAN Jian-de;ZHOU Wei-wei;MIAO Bing-lin;XU Long;ZHOU Li-ping(Chemical Pharmaceutical Research Institute,Taizhou Vocational&Technical College,Taizhou 318000,China;Taizhou Dachen Pharmaceutical Co.,Ltd.,Linhai 317016,China)

机构地区：[1]台州职业技术学院化学制药研究所,浙江台州318000 [2]台州达辰药业有限公司,浙江临海317016

出　　处：《精细化工中间体》2022年第3期23-26,共4页Fine Chemical Intermediates

基　　金：台州市科技计划项目(21gyb24);浙江省教育厅高等学校访问工程师校企合作项目(FG2020223)。

摘　　要：水合肼(2)经三氟乙酸乙酯和氯乙酰氯取代反应,Vilsmeier试剂关环,得中间体3,再经乙二胺取代,盐酸乙醇关环制得西他列汀关键中间体3-三氟甲基-5,6,7,8-四氢-1,2,4-三唑-[4,3-a]并吡嗪盐酸盐(1),其结构经H NMR和MS确证,总收率达55%。此反应条件温和,同时避免含磷废水产生,更适合工业化生产。Using hydrazine hydrate(2)as the raw material,compound 3 was obtained through the reaction with ethyl trifluoroacetate,then chloracetylation,cyclization using Vilsmeier reagent.Compound 3 was subjected to ethylendiamine,dehydration and recyclization under hydrochloric acid to obtain the key intermediate of sitagliptin(1)in an overall yield of 55%.The structures of the intermediate and product were characterized by~1H NMR and MS spectra.The advantages of this present process include mild reaction condition and avoiding phosphorus wastewater.Therefore it is promising for industrial application.

关 键 词：西他列汀 关键中间体 脱水 合成 

分 类 号：TQ246.3[化学工程—有机化工]