(R)-3-(3-氟-4-吗啉苯基)-2-氧-5-噁唑烷基甲醇的合成  

Synthesis of (R)-3-(3-Fluoro-4-morpholinylphenyl)-2- oxo-5-oxazolidinylmethanol

作　　者：庞华[1] 张君仁[2] 王子兰[1] 冉祥凯[1] 杜金[1] 

机构地区：[1]山东大学化学与化工学院,山东济南250012 [2]山东大学药学院,山东济南250012

出　　处：《精细化工》2004年第1期70-71,75,共3页Fine Chemicals

基　　金：山东省卫生厅项目基金资助(05210209)

摘　　要：以3,4 二氟硝基苯为原料,与吗啉在二异丙基乙胺中反应4h得到3 氟 4 吗啉硝基苯(Ⅰ),在w(Pd)=10%催化下,Ⅰ与甲酸铵在V(THF)∶V(甲醇)=1∶4中反应6h,得3 氟 4 吗啉苯胺(Ⅱ),Ⅱ与光气在通入干燥HCl气体下反应得3 氟 4 吗啉异氰酸苯酯(Ⅲ),最后在无水LiBr和n Bu3PO催化下,Ⅲ与(R) 丁酸缩水甘油酯在二甲苯中反应2h,所得产物在甲醇钠催化下,与甲醇反应3h,合成了(R) 3 (3 氟 4 吗啉苯基) 2 氧 5 口恶唑烷基甲醇(Ⅳ),总收率35 8%。3-Fluoro-4-morpholinylnitrobenzene(Ⅰ) was prepared by reaction of 3,4-difluoronitrobenzene and morpholine in diisopropylethylamine for 4 h.Catalyzed by Pd/C 〔w(Pd)=10%〕,Ⅰreacted with ammonium formate in mixed solvent 〔V(THF)∶V(methanol)=1∶4〕 for 6 h to afford 3-fluoro-4-morpholinylaniline(Ⅱ).Then the interaction of Ⅱ and phosgene in dry hydrogen chloride gas gave 3-fluoro-4-morpholiylphenyl isocyanate(Ⅲ).Finally the reaction of Ⅲ with (R)-glycidyl butyrate catalyzed by anhydrous LiBr and tri-n-butylphosphine oxide in xylene for 2 h gave a new product,which was catalyzed by sodium methoxide and reacted with methanol for 3 h to synthesize (R)-3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinylmethanol(Ⅳ).The overall yield was 35.8%.

关 键 词：(R)-3-(3-氟-4-吗啉苯基)-2-氧-5-噁唑烷基甲醇 利奈唑酮 噁唑烷 

分 类 号：R979.1[医药卫生—药品]