阿维巴坦钠工艺杂质的合成研究  

Synthesis of Impurity in Avibactam Sodium

作　　者：钟霞[1] 陈年根[1] 

机构地区：[1]海南医学院药学院,海南海口571199

出　　处：《化学试剂》2017年第8期884-886,894,共4页Chemical Reagents

基　　金：海南省自然科学基金资助项目(814287);国家级大学生创新实验项目(201511810003);海南医学院大学生创新实验项目(HYCX2014007)

摘　　要：研究了阿维巴坦钠工艺杂质的合成工艺,以便对阿维巴坦钠的质量进行控制。以(2S,5R)-5-[(苄基氧基)氨基]哌啶-2-甲酸乙酯草酸盐为起始原料,经缩合、水解、磺酰胺化、脱保护、磺酰化、盐交换等反应制备(2S,5R)-7-氧代-N-磺酸基-6-磺酸氧基-1,6-二氮杂双环[3.2.1]辛烷-2-甲酰胺二钠盐。目标产物的化学结构经质谱、~1HNMR和^(13)CNMR等确证,纯度为99.3%,总收率为15.7%(以原料计算)。该工艺反应条件温和、操作简便,为阿维巴坦钠工艺杂质的合成提供了一种新选择。To conduct the quality control of avibactam sodium, the impurity （ 2S, 5R） -7-oxo-N-sulfo-6-sulfooxy- 1,6-diazabicyclo [ 3.2. 1]octane-2-carboxamidedisodium salt generated in the synthetic process of avibactam sodium was synthesized.The impurity was synthesized from （2S, 5R）-ethyl 5-（benzyloxyarnino） piperidine-2-carboxylate oxalate as raw material via condensation, hy- drolysis,sulfonamidation ,deprotection of benzyl group,sulfonylation and base replacement.The results showed that the purity was 99.3%, and the total yield was 15.7%.The chemical structure was confirmed by MS, 1HNMR and 13CNMR .The process was sim- ple and a new choice for production of the process impurity inavibactam sodium.

关 键 词：阿维巴坦钠 Β-内酰胺酶抑制剂 工艺杂质 

分 类 号：O643.3[理学—物理化学]