(R)-N-[[3-[3-氟-4-吗啉基]苯基]-2-氧代-5-噁唑烷基]甲醇的合成  

Synthesis of(R)-N-[[3-[3-Fluoro-4-morpholinyl] phenyl]-2-oxo-5-oxazolidinyl]Methanol

作　　者：李云[1] 黄长江[1] 高慧[2] 高维娜[2] 刘登科[1] 徐为人[1] 杜奇石[2] 魏冬青[2] 

机构地区：[1]天津药物研究院,天津300193 [2]天津师范大学生物信息与药物开发研究所,天津300074

出　　处：《天津师范大学学报（自然科学版）》2005年第4期13-15,共3页Journal of Tianjin Normal University：Natural Science Edition

基　　金：天津市科委基础科学重点资助项目(033801911)

摘　　要：利奈唑酮是新上市的一种口恶唑烷酮类全合成抗菌药,本研究对其关键中间体(R)-N-[[3-[3-氟-4-吗啉基]苯基]-2-氧代-5口-恶唑烷基]甲醇(1)的合成方法做了改进.合成3-氟-4-吗啉基硝基苯时,用价廉易得的三乙胺代替二异丙基乙胺,反应时间由72h缩短到6h;合成3-氟-4-吗啉基苯胺时,将溶媒改为丙酮,采用Pd/C(10%)还原,反应液直接与氯甲酸苄酯反应制得N-苄氧羰基-3-氟-4-吗啉基苯胺,实现了两步合一,收率提高到93.2%;合成(1)时,反应温度提高到-50℃左右,实验条件较文献方法相对温和.Linezolid is a synthetic oxazolidinones antibacterial agent which has been marketed recently. The synthetic methods reported by literature was modified and its key intermediate （R）-N-[3-[-3 fluoro-4- morpholinyl-]phenyl-]-2-oxo-5-oxazolidinyl-]methanol （1）was successfully synthesized. With cheap triethylamine substituting for N,N-diisopropylethylamine to prepare 3-fluoro-4-morpholinylnitrobenzene,the reaction time curtailed from 72h to 6h; By using Pd/C（10%） as deoxidizer in acetone, the solution reacted with benzyl chloroformate directly to prepare N-carbobenzoxy-3-fluoro-4-morpholinylaniline, which merged two steps into one and got excellent yield（93.2%）. When preparing compound（1）, the temperature was raised to approximate -50℃ ,making the condition milder than that of literature.

关 键 词：噁唑烷酮 利奈唑酮 工艺改进 

分 类 号：O6[理学—化学]