度洛西汀中间体手性拆分工艺的研究  

Technics Study on Chiral Separation of Duloxetine Intermediate

作　　者：刘艳梅[1] 刘杰 李海华[1] 刘娅静[1] 陈晓超[1] 官儒奇[1] 赵亚娟[1] 

机构地区：[1]温州大学化学与材料工程学院,浙江温州325027 [2]中国昆仑工程公司辽宁分公司,辽宁沈阳111003

出　　处：《化工技术与开发》2014年第4期28-31,共4页Technology & Development of Chemical Industry

基　　金：浙江省重中之重化学一级学科(316406125020301);浙江省公益技术应用研究计划项目(2013C31129)的资助

摘　　要：以噻吩和3-氯丙酰氯为原料,经傅克反应生成3-氯-1-(2-噻吩)-丙酮,用硼氢化钠加氢还原得到混旋的度洛西汀中间体3-氯-1-(2-噻吩)-丙醇中间体。利用D-扁桃酸为拆分剂对其中间体进行手性拆分得到较纯的(S)-3-氯-1-(2-噻吩)-丙醇。实验结果表明,3-氯-1-(2-噻吩)-丙醇与D-扁桃酸摩尔的量的比值为主要因素,析出晶体温度和溶剂为次要因素。以苯为溶剂时,3-氯-1-(2-噻吩)-丙醇与D-扁桃酸的量的摩尔比值为1∶0.4,析出温度为0℃,拆分效果较好,其o.p.值为74%。Starting from thiophene and 3-chloropropinylchloride, 3-chloro-1-（2-thienyl）propanone was prepared by Friedel-Crafts reaction. Then using sodium borohydride, 3-chloro-1-（2-thienyl）propanol was prepared through hydrogenation reduction. Through chiral separation, the relatively pure product （S）-3-chloro-1-（2-thienyl）propanol was got. The results of experiment indicated that the molar ratio of 3-chloro-1-（2-thienyl）propanol to D-（-）-mandelic acid was the main factor, and the crystallized temperature and the solvent were secondary factors. When the solvent was benzene and the molar ratio of D-（-）-mandelic acid to 3-chloro-1-（2-thienyl） propanol was 0.4：1, the crystallized temperature was 0℃, the better results of separation was got, the value of o.p. （optical purity） was 74%.

关 键 词：抗抑郁药 度洛西汀中间体 手性拆分 

分 类 号：O626.12[理学—有机化学]