(S)-N-环氧丙基邻苯二甲酰亚胺的合成

Synthesis of(S)-N-Glycidyl Phthalimide

本研究报道了一种利奈唑胺和利伐沙班的关键中间体(S)-N-环氧丙基邻苯二甲酰亚胺的合成方法。(S)-3-氨基-1,2-丙二醇与邻苯二甲酸酐在乙酸乙酯中缩合得2-[(2S)-2,3-二羟基丙基]异吲哚-1,3-二酮(4),4的伯羟基选择性与对甲苯磺酰氯反应后,再在氢氧化钠作用下闭环得目标化合物,总收率77.9%,纯度99.9%,光学纯度99.2%。本方法操作便捷、条件温和、产品纯度高。

A synthetic method for （S）-N-glycidyl phthalimide, the key intermediate of linezolid and rivaroxaban, was reported. 2-[（2S）-2,3-Dihydroxypropyl）isoindole-1,3-dione （4） was obtained from （S）-3-aminopropane-1,2-diol via condensation with o-phthalic anhydride in ethyl acetate. The primary hydroxyl group of 4 reacted with tosyl chloride selectively followed by the ring-closure in the presence of sodium hydroxide solution to prepare the target compound with a total yield of 77.9%, a purity of 99.9% and optical purity of 99.2%. This synthetic route has advantages of simple operation, mild condition and high purity, which are more suitable for large-scale production.