“一锅法”制备瑞德西韦中间体  

One-pot synthetic method of intermediate of remdesivir

作　　者：张燕梅 赖庆富 叶连宝 高伟 陈伟强 罗艳 ZHANG Yanmei;LAI Qingfu;YE Lianbao;GAO Wei;CHEN Weiqiang;LUO Yan(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Nursing,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广东药科大学药学院,广东广州510006 [3]广东药科大学护理学院,广东广州510006

出　　处：《广东药科大学学报》2021年第4期14-16,共3页Journal of Guangdong Pharmaceutical University

基　　金：广东普通高校新冠肺炎疫情防控科研专项(2020KZDZX1131);2020年广东省研究生教育创新计划-广东省联合培养研究生示范基地项目。

摘　　要：目的对瑞德西韦中间体的制备工艺进行改进。方法以L-丙氨酸2-乙基丁基酯盐酸盐、二氯磷酸苯酯、五氟苯酚为原料,通过"一锅法"经磷酰化反应得到瑞德西韦中间体(2S)-2-(((2,3,4,5,6-五氟苯氧基)(苯氧基)磷酰基)氨基)丙酸2-乙基丁基酯。结果目标化合物经^(1)H NMR、^(13)C NMR、^(19)F NMR、MS确认结构,总产率为73%,纯度99.8%。结论本方法可为(2S)-2-(((2,3,4,5,6-五氟苯氧基)(苯氧基)磷酰基)氨基)丙酸2-乙基丁基酯的工业化生产提供参考。Objective To improve the preparation process of the intermediate of remdesivir.Methods The intermediate of remdesivir(2 S)-2-(((2,3,4,5,6-pentafluoro-phenoxy)(phenoxyl)phosphoryl)amino)propionic acid 2-ethylbutyl ester was synthesized from L-alanine 2-ethyl butyl ester hydrochloride,phenyl dichlorophosphate and pentafluorophenol as raw materials by phosphorylation through"one-pot process".Results The structure of the target compound was confirmed by ^(1)HNMR,^(13)CNMR,^(19)F NMR and MS.The overall yield of the compound was 73%and the purity was 99.8%.Conclusion This article provides a more reasonable route for the synthesis of(2 S)-2-(((2,3,4,5,6-pentafluoro-phenoxy)(phenoxyl)phosphoryl)amino)propionic acid 2-ethylbutyl ester.

关 键 词：瑞德西韦 中间体 (2S)-2-(((2 3 4 5 6-五氟苯氧基)(苯氧基)磷酰基)氨基)丙酸2-乙基丁基酯 合成 

分 类 号：R914.5[医药卫生—药物化学]