(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(E)-3-(4-fluorophenyl)-2-propenyl]-2-azetidinone -Drug Synthesis Database

【结构式】

【分子编号】37696

【品名】(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(E)-3-(4-fluorophenyl)-2-propenyl]-2-azetidinone

【CA登记号】

【分子式】C₃₁H₂₅F₂NO₂

【分子量】481.5418464

【元素组成】C 77.32% H 5.23% F 7.89% N 2.91% O 6.65%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XXX)

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.

参考文献中间体

合成目标

【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：(VII)

参考文献中间体

合成目标

【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

Extended Information