利奈唑胺的合成

Synthesis of Linezolid

以吗啡啉和3,4-二氟硝基苯为原料,经取代、还原、重氮化和桑德迈尔反应合成中间体3-氟-4-吗啉基溴苯(Ⅳ);以(R)-环氧氯丙烷、氰酸钾为原料经加成、取代反应合成中间体(R)-5-邻苯二甲酰亚胺甲基-2-口恶唑烷酮(Ⅵ)。将Ⅳ和Ⅵ通过缩合、水解合成产物利奈唑胺。产物结构通过1HNMR及LC-MS进行了表征。探讨了中间体Ⅱ、Ⅳ、Ⅵ、Ⅶ、Ⅰ合成工艺的影响因素,优化后反应总收率为24.6%。

The key intermediate 3-fluoro-4-morpholin-4-yl-phenylamine （Ⅳ） was synthesized from morpholine and 3,4-difluoronitrobenzene by substitution, reduction, diazotization and Sandmeyer reaction. （R）-Epichlorohydrin reacted with potassium cyanate by addition and substitution to get intermediate （R） -5- （ N-methyl phthalimide-yl） -2-oxazolidinone （ Ⅵ ）. Finally, Ⅳ reacted with Ⅵ via condensation, hydrolysis to afford the target compound linezolid. The chemical structure of the target product was confirmed by ^1HNMR and LC-MS. The influencing factors of intermediate Ⅱ , Ⅳ, Ⅵ, Ⅶ and target compound in the synthetic reactions were investigated. The optimized overall yield was 24.6% ,which was superior to literature.