甲氧依托咪酯盐酸盐杂质PIM-A的合成

Synthesis of impurity PIM-A in Methoxyetomidate hydrochloride

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.