抗抑郁药艾司西酞普兰的合成工艺改进  

Process Improvement on The Synthesis of Antidepressant Escitalopram

作　　者：龙超久 游勇 周鸣强 周先礼[1] 

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610031 [2]成都丽凯手性技术有限公司,四川成都610041 [3]中国科学院成都有机化学研究所,四川成都610041

出　　处：《合成化学》2018年第2期135-139,共5页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21602217)

摘　　要：报道了一种抗抑郁药艾司西酞普兰(1)的合成工艺改进。以消旋的4-二甲基氨基-1-(4-氰基-2-羟甲基苯基)-1-(4-氟苯基)-1-丁醇为原料,经D-(+)-二对甲基苯甲酰酒石酸拆分、环合合成1,其结构经1H NMR和13C NMR确证。通过将拆分母液中残留的R-构型原料经分离、在硫酸作用下发生构型翻转并环合的方法,提高了1的收率(成盐产物总收率45.4%,光学纯度98.9%)。A method for process improvement of antidepressant Escitalopram( 1) was reported. 1 was synthesized from recemic 4-[4-( dimethylamino)-1-( 4-fluorophenyl)-1-hydroxybutyl]-3-( hydroxymethyl) benzonitrile by the optical resolution with D-DTTA,cyclization and salification. The structure was confirmed by1 H NMR and13 C NMR. Due to the separation of residual material of R-configuration in the mother liquid,configuration inversion with sulfuric acid and cyclization,the yield of escitalopram was improved( yield of 45. 4% and optical purity of 98. 9%).

关 键 词：抗抑郁药 艾司西酞普兰 手性拆分 合成 工艺改进 

分 类 号：O626.1[理学—有机化学] R914.5[理学—化学]