唑来膦酸的工业合成  

Industrial Synthesis of Zoledronic Acid

作　　者：徐桂清[1] 李富志[2] 郝二军[1] 韩凌[1] 袁明贵[1] 李伟[1] 

机构地区：[1]河南师范大学化学与环境科学学院,河南新乡453007 [2]河南天方药业股份有限公司,河南驻马店463000

出　　处：《河南师范大学学报（自然科学版）》2009年第5期160-161,164,共3页Journal of Henan Normal University(Natural Science Edition)

基　　金：河南省科技攻关计划项目(82102330029);河南师范大学青年科学基金(2008qk11)

摘　　要：以咪唑为起始原料,和氯乙酸乙酯经N-烷基化、水解、成盐得2-(1-咪唑基)乙酸盐酸盐(4),4再与磷酸、三氯化磷反应,然后精制得唑来膦酸(1),总收率为30.4%.合成的目标化合1,其结构经核磁共振氢谱、红外光谱、质谱及元素分析确证.与文献相比,改进后的路线操作简便,易于工业化,制得的产品纯度高.Zoledronic acid is prepared from imidazole via N--alkylation with ethyl bromoacetate, followed by hydrolysis and salification to give 2-（1-imidazoly） acetic acid hydrochloride which is reacted with phosphoric acid and PCI3 to give the target compound. The overall yield is 30.4%. The structure of the target compound is confirmed by 1H-NMR,IR,MS and elemental analysis. Compared with the literature process, the improved method is more convenient and the purity of zoledronie acid is more than 99 %.

关 键 词：唑来膦酸 工业合成 咪唑 氯乙酸乙酯 

分 类 号：R979.9[医药卫生—药品]