【结 构 式】 |
【分子编号】37695 【品名】(4S)-3-[(2R,4E)-2-[(S)-[4-(benzyloxy)phenyl](4-fluoroanilino)methyl]-5-(4-fluorophenyl)-4-pentenoyl]-4-phenyl-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C40H34F2N2O4 【 分 子 量 】644.7178464 【元素组成】C 74.52% H 5.32% F 5.89% N 4.35% O 9.93% |
合成路线1
该中间体在本合成路线中的序号:(XXIX)6) The reaction of 5-(4-fluorophenyl)-4-pentenoic acid (XXVI) with oxalyl chloride gives the acyl chloride (XXVII), which is condensed with the chiral oxazolidinone (XXI) by means of DMAP and DIEA in dichloromethane, yielding the acyloxazolidinone (XXVIII). Condensation of (XXVIII) with the benzylideneimine (II) by means of TiCl4 affords adduct (XXIX), which is cyclized to the chiral azetidinone (XXX). The oxidation of the double bond of (XXX) with benzoquinone and HClO4 catalyzed by Pd(OAc)2 in acetonitrile/water provides the previously reported trans-(3R,4S)-azetidinone (XX), which is worked up to give azetimibe as described before.
【1】 Castañer, R.M.; Sorbera, L.A.; Castañer, J.; Ezetimibe. Drugs Fut 2000, 25, 7, 679. |
【2】 Shankar, B.B. (Schering Corp.); Process for preparing 1-(4-fluorophenyl)-3(R)-(3(S)-hydroxy-3-([phenyl or 4-fluorophenyl])-propyl)-4(S)-(4-hydroxyphenyl)-2-azetidinone. US 5856473; WO 9716424 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II) | 37689 | N-[(Z)-[4-(benzyloxy)phenyl]methylidene]-4-fluoroaniline; N-[(Z)-[4-(benzyloxy)phenyl]methylidene]-N-(4-fluorophenyl)amine | C20H16FNO | 详情 | 详情 | |
(XX) | 20656 | (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]-2-azetidinone | C31H25F2NO3 | 详情 | 详情 | |
(XXI) | 12173 | (4S)-4-Phenyl-1,3-oxazolan-2-one; (4S)-4-Phenyl-2-oxazolidinone; (S)-(+)-4-Phenyl-2-oxazolidinone | 99395-88-7 | C9H9NO2 | 详情 | 详情 |
(XXVI) | 37692 | (E)-5-(4-fluorophenyl)-4-pentenoic acid | 190595-67-6 | C11H11FO2 | 详情 | 详情 |
(XXVII) | 37693 | (E)-5-(4-fluorophenyl)-4-pentenoyl chloride | C11H10ClFO | 详情 | 详情 | |
(XXVIII) | 37694 | (4S)-3-[(E)-5-(4-fluorophenyl)-4-pentenoyl]-4-phenyl-1,3-oxazolidin-2-one | C20H18FNO3 | 详情 | 详情 | |
(XXIX) | 37695 | (4S)-3-[(2R,4E)-2-[(S)-[4-(benzyloxy)phenyl](4-fluoroanilino)methyl]-5-(4-fluorophenyl)-4-pentenoyl]-4-phenyl-1,3-oxazolidin-2-one | C40H34F2N2O4 | 详情 | 详情 | |
(XXX) | 37696 | (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(E)-3-(4-fluorophenyl)-2-propenyl]-2-azetidinone | C31H25F2NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(VI)
【1】 Rosenblum SB, Dugar S,Bumett DA et al.1995. Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents.W0 9508532(本专利属于Schering Corporation. USA) |
【2】 Shankar BB. 1999. Process for preparing l-(4-fluorophenyD-3(R),[3(S)-hydroxy-3-[(phenylor 4-flu-orophenyl)]-propyll-4 (S) -(4-hydroxyphenyD-2-azetidinone US 5856473(本专利属于Scherirra: Corporation, USA) |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 37692 | (E)-5-(4-fluorophenyl)-4-pentenoic acid | 190595-67-6 | C11H11FO2 | 详情 | 详情 |
(II) | 37693 | (E)-5-(4-fluorophenyl)-4-pentenoyl chloride | C11H10ClFO | 详情 | 详情 | |
(III) | 12173 | (4S)-4-Phenyl-1,3-oxazolan-2-one; (4S)-4-Phenyl-2-oxazolidinone; (S)-(+)-4-Phenyl-2-oxazolidinone | 99395-88-7 | C9H9NO2 | 详情 | 详情 |
(IV) | 37694 | (4S)-3-[(E)-5-(4-fluorophenyl)-4-pentenoyl]-4-phenyl-1,3-oxazolidin-2-one | C20H18FNO3 | 详情 | 详情 | |
(V) | 37689 | N-[(Z)-[4-(benzyloxy)phenyl]methylidene]-4-fluoroaniline; N-[(Z)-[4-(benzyloxy)phenyl]methylidene]-N-(4-fluorophenyl)amine | C20H16FNO | 详情 | 详情 | |
(VI) | 37695 | (4S)-3-[(2R,4E)-2-[(S)-[4-(benzyloxy)phenyl](4-fluoroanilino)methyl]-5-(4-fluorophenyl)-4-pentenoyl]-4-phenyl-1,3-oxazolidin-2-one | C40H34F2N2O4 | 详情 | 详情 | |
(VII) | 37696 | (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(E)-3-(4-fluorophenyl)-2-propenyl]-2-azetidinone | C31H25F2NO2 | 详情 | 详情 | |
(VIII) | 37688 | (3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]-4-(4-hydroxyphenyl)-2-azetidinone | C24H19F2NO3 | 详情 | 详情 | |
(IX) | 20631 | (R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-83-0 | C18H20BNO | 详情 | 详情 |