依泽替米贝合成工艺研究  

Study on synthetic technology of ezetimibe

作　　者：严宾 袁拥军 

机构地区：[1]精华制药集团南通有限公司,江苏南通226407

出　　处：《现代医药卫生》2015年第24期3712-3713,3716,共3页Journal of Modern Medicine & Health

摘　　要：目的研究依泽替米贝合成方法 ,并对合成工艺进行优化。方法以3-(3-[2-氧代-4-(苄氧苯基)-1-(4-氟苯基)-氮杂环丁烷基])丙酸为原料,经酰氯化,与格氏试剂偶联,手性还原,氢化脱苄基反应得到依泽替米贝。并对依泽替米贝合成条件进行优化。结果经过优化使得依泽替米贝合成总收率提升至52.3%,纯度达99.8%。结论该法操作简单,反应条件温和,产品收率和纯度高,且合成得到的依泽替米贝结构经质谱和核磁共振证实。Objective To study the synthetic process for ezetimibe and to optimize its synthetic technology. Methods3-（3-（2-oxygen generation-4-（benzyloxyphenyl）-1-（4-fluorophenyl）-nitrogen heterocyclic butyl alkyl]） propionic acid served as the raw material,after acyl chlorination,which was coupled with Grignard reagent,then performed the chiral reduction and hydrogenated debenzylation for obtaining ezetimibe. The synthetic conditions were optimized. Results The total yield rate of ezetimibe was increased to 52.3% after optimization and the purity was up to 99.8%. Conclusion This process is simple with mild reaction condition,high product yield rate and high purity, moreover the structure of synthesized ezetimibe is verified by the mass spectrometry（MS） and nuclear magnetic resonance（NMR）.

关 键 词：吖丁啶类 抗胆固醇血症药 依泽替米贝 合成 条件优化 

分 类 号：R541.4[医药卫生—心血管疾病]