摘要
盐酸氟西汀是一种临床广泛使用的非三环类抗抑郁药,本工作介绍了一种不对称合成(S)-和(R)-盐酸氟西汀的方法.以自制的手性噁唑硼烷为催化剂,将起始原料β-氯苯丙酮不对称催化氢化还原成(S)-或(R)-手性醇,这一步的化学收率和光学收率都较高.然后再经两步,(S)-和(R)-手性醇转化为(S)-和(R)-盐酸氟西汀.整个工艺只需三步,总收率为66.5%,盐酸氟西汀对映体的ee值可达98.6%.还考察了反应温度、溶剂、催化剂的量等因素对β-氯苯丙酮的不对称氢化还原的化学产率和光学收率的影响.
The enantioselective synthesis of fluoxetine hydrochloride, a potent serotonin-uptake inhibitor, was described. The asymmetric reduction of 3-chloropropiophenone catalyzed by chiral oxazaborolidines enantioselectively gave S- or R-3-chloro-l-phenylpropanol （2） in good yield. In following two steps, alcohol 2 was converted into S- or R-fluoxetine hydrochloride in 66.5% overall yield and 98.6% ee. Some factor effecting the yield and the enantioselectivity of asymmetric reduction of 3-chloropropiophenone was investigated.
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2006年第1期65-68,共4页
Chinese Journal of Organic Chemistry
基金
江苏省科技厅自然科学基金(No.BK2005045)
江苏省教育厅高校自然科学计划(No.05KJD150024)资助项目.
关键词
盐酸氟西汀
制剂
手性嗯唑硼烷
不对称还原
fluoxetine hydrochloride
inhibitor
chiral oxazaborolidine
asymmetric reduction
