依替米贝合成新工艺的研究余长泉.pdfVIP

26 6 No.6 Vol.26 2012 12 Journal of Chemical Engineering of Chinese Universities Dec. 2012 1003-9015(2012)06-1014-06  , ( 310027) (Ezetimibe) 4-4- N-(4-)-4-( 2)4-(4-) (S)-4-- CBS/BH3 (4S)-3-[(5S)-5-(4-)-5- i -1-]-4--2-( 4) 2 TiCl (O Pr) 2 2 Pa/C 92.4%×91.6%×77.7%×85.3% = 56% 1 MS H-NMR R972 TQ460.3 A DOI 10.3969/j.issn.1003-9015.2012.06.018 New Synthesis Process for the Synthesis of Ezetimibe YU Chang-quan, YANG Jian (Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China) Abstract: Ezetimibe is a novel selective cholesterol absorption inhibitor which was developed by both Schering-Plough and Merck. An improved process for the preparation of ezetimibe was studied and was described as follows. N-(4-(benzyloxy)benzylidene)-4-fluorobenzenamine (Compound 2) was prepared from 4-hyd- roxybenzaldehyde, 4-fluorobenzenamine and benzyl chloride in one pot. 5-(4-Fluorophenyl)-5-oxopentanoic acid was reacted with pivaloyl chloride and directly condensed with (S)-4-phenyloxazolidin-2-one promoted with LiCl, and then reduced by CBS/BH3 to get (4S)-3-[(5S)-5-(4-fluoror)-5-hydrox-1-oxo-pentyl]-4-phenyl- oxazolidin-2-one (Compound 4). It was condensed with compound 2 catalyzed with Lewis acid after being