甲氧依托咪酯盐酸盐杂质PIM-A的合成  

Synthesis of impurity PIM-A in Methoxyetomidate hydrochloride

作　　者：刘良权 杨俊[2] 齐庆蓉[1] LIU Liangquan;YANG Jun;QI Qingrong(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;West China School of Medicine,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041 [2]四川大学华西临床医学院,四川成都610041

出　　处：《华西药学杂志》2021年第4期367-370,共4页West China Journal of Pharmaceutical Sciences

基　　金：四川省重点研发项目(批准号:2019YFS0093)。

摘　　要：目的合成甲氧依托咪酯盐酸盐制备工艺过程中产生的杂质PIM-A。方法以3-羟基苯乙酮及苄溴作为起始原料,经醚化、还原、Mitsunobu反应、水解、取代及催化氢化等6步反应,制备得到目标化合物PIM-A。结果得到PIM-A,总收率为3.56%,并通过NMR、ESI-MS、HMQC及HMBC谱确证其结构。结论制备的PIM-A可作为甲氧依托咪酯盐酸盐的杂质对照品。该方法反应条件温和、原料易得、操作简单、实用性较强。OBJECTIVE To synthesize PIM-A,an impurity in the preparation of Methoxyetomidate hydrochloride.METHODS 3-hydroxyacetophenone and benzyl bromide were used as starting materials and the target compound was synthesized via etherification,reduction,Mitsunobu reaction,hydrolysis,substitution,and catalytic hydrogenation.RESULTS The target compound PIM-A was synthesized with total yield 3.56%.Finally,the structure of PIM-A was verified by NMR,ESI-MS,HMQC and HMBC spectra.CONCLUSION PIM-A can be used as the impurity reference of methoxy-etomidate hydrochloride.The synthesis method shows mild reaction conditions,easily obtained raw materials,simple operation and strong practicability.

关 键 词：甲氧依托咪酯盐酸盐 杂质 3-羟基苯乙酮 MITSUNOBU反应 核磁共振 HMQC谱 HMBC谱 杂质对照品 

分 类 号：R914[医药卫生—药物化学]