(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one -Drug Synthesis Database

【结构式】

【分子编号】53477

【品名】(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one

【CA登记号】n/a

【分子式】C₂₀H₂₀FNO₄

【分子量】357.3815432

【元素组成】C 67.22% H 5.64% F 5.32% N 3.92% O 17.91%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The enantioselective reduction of the oxazolidinone (I) with BH3/SMe2 and a chiral borinated catalyst gives the (S)-alcohol (II), which is condensed with the labeled imine (III) (prepared by reaction of 4-fluoroaniline (IV) and 13C-labeled 4-hydroxybenzaldehyde (V)) by means of TiCl4 in dichloromethane to yield the silylated adduct (VI) (previously the reactants are silylated with Tms-Cl and DIEA). Finally, adduct (VI) is resilylated with bis(trimethylsilyl)acetamide and cyclized and desilylated by treatment with TBAF in dichloromethane to afford the target 13C-labeled SCH-58235.

参考文献中间体

合成目标

【1】 Hesk, D.; et al.; Synthesis of 3H, 14C and 13C6 labelled Sch 58235. J Label Compd Radiopharm 2002, 45, 2, 145.

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)	53476	1-(4-fluorophenyl)-5-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-1,5-pentanedione	n/a	C₂₀H₁₈FNO₄	详情	详情
(II)	53477	(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one	n/a	C₂₀H₂₀FNO₄	详情	详情
(III)	53478		n/a	C₁₃H₁₀FNO	详情	详情
(III)	53481	4-{[(4-fluorophenyl)imino]methyl}phenol	3382-63-6	C₁₃H₁₀FNO	详情	详情
(IV)	37690	4-fluorophenylamine; 4-fluoroaniline	371-40-4	C₆H₆FN	详情	详情
(V)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(V)	53479		n/a	C₇H₆O₂	详情	详情
(VI)	16734	(2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₄	详情	详情
(VI)	53480		n/a	C₃₇H₄₀F₂N₂O₇SSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The enantioselective reduction of the oxazolidinone (I) with BH3/SMe2 and a chiral borinated catalyst gives the (S)-alcohol (II), which is condensed with the labeled imine (III) (prepared by reaction of 4-fluoroaniline (IV) and 14C-labeled 4-hydroxybenzaldehyde (V)) by means of TiCl4 in dichloromethane to yield the silylated adduct (VI) (previously the reactants are silylated with Tms-Cl and DIEA). Finally, adduct (VI) is resilylated with bis(trimethylsilyl)acetamide and cyclized and desilylated by treatment with TBAF in dichloromethane to afford the target 14C-labeled SCH-58235.

参考文献中间体

合成目标

【1】 Hesk, D.; et al.; Synthesis of 3H, 14C and 13C6 labelled Sch 58235. J Label Compd Radiopharm 2002, 45, 2, 145.

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)	53476	1-(4-fluorophenyl)-5-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-1,5-pentanedione	n/a	C₂₀H₁₈FNO₄	详情	详情
(II)	53477	(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one	n/a	C₂₀H₂₀FNO₄	详情	详情
(III)	53481	4-{[(4-fluorophenyl)imino]methyl}phenol	3382-63-6	C₁₃H₁₀FNO	详情	详情
(III)	53484		n/a	C₁₃H₁₀FNO	详情	详情
(IV)	37690	4-fluorophenylamine; 4-fluoroaniline	371-40-4	C₆H₆FN	详情	详情
(V)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(V)	53483	4-hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(VI)	53482	(1S,4R,5S)-5-(4-fluoroanilino)-1-(4-fluorophenyl)-4-{[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]carbonyl}-5-{4-[(trimethylsilyl)oxy]phenyl}pentyl methanesulfonate	n/a	C₃₇H₄₀F₂N₂O₇SSi	详情	详情
(VI)	53485		n/a	C₃₇H₄₀F₂N₂O₇SSi	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

The activation of 5-(4-fluorophenyl)-5-oxopentanoic acid (I) with pivaloyl chloride (II) gives the mixed anhydride (III), which is condensed with the chiral oxazolidinone (IV) by means of DMAP to yield the acylated oxazolidine (V) (1). The asymmetric reduction of (V) by means of BH3/Me2S catalyzed by the chiral boron catalyst (VI) affords the chiral alcohol (VII) (1-3), which is condensed with the imine (VIII) by means of Tms-Cl, DIEA and TiCl4 to provide the adduct (IX). The cyclization of (IX) by means of bis(trimethylsilyl)acetamide and TBAF gives the protected azetidinone (X), which is finally desilylated by means of sulfuric acid in isopropanol

参考文献中间体

合成目标

【1】 Fu, X.Y.; et al.; Process for preparing ezetimibe intermediate by an acid enhanced chemo- and enantioselective CBS catalyzed ketone reduction. Tetrahedron Lett 2003, 44, 4, 801.
【2】 Thiruvengadam, T.K.; Tann, C.-H.; Fu, X.; McAllister, T.L. (Schering Corp.); Enantioselective synthesis of azetidinone intermediate cpds.. US 2002193607; WO 0279174 .

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)	62208	4-(4-Fluorobenzoyl)butyric acid; 4-(4-fluorobenzoyl) butyric acid; 4-(4'-Fluorobenzoyl)butyric acid; 4-(p-Fluorobenzoyl) butyric acid; 5-(4'-Fluorophenyl)-5-oxopentanoic acid	149437-76-3	C₁₁H₁₁FO₃	详情	详情
(II)	13597	2,2-Dimethylpropanoyl chloride; Pivaloyl chloride	3282-30-2	C₅H₉ClO	详情	详情
(III)	62209	1,1-dimethylpropanoic 4-(4-fluorophenyl)-4-oxopentanoic anhydride		C₁₆H₁₉FO₄	详情	详情
(IV)	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
(V)	53476	1-(4-fluorophenyl)-5-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-1,5-pentanedione	n/a	C₂₀H₁₈FNO₄	详情	详情
(VI)	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
(VII)	53477	(4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one	n/a	C₂₀H₂₀FNO₄	详情	详情
(VIII)	62210	4-fluoro-N-((Z)-{4-[(trimethylsilyl)oxy]phenyl}methylidene)aniline; N-(4-fluorophenyl)-N-((Z)-{4-[(trimethylsilyl)oxy]phenyl}methylidene)amine		C₁₆H₁₈FNOSi	详情	详情
(IX)	62211	(4S)-3-{(2R,5S)-2-((S)-(4-fluoroanilino){4-[(trimethylsilyl)oxy]phenyl}methyl)-5-(4-fluorophenyl)-5-[(trimethylsilyl)oxy]pentanoyl}-4-phenyl-1,3-oxazolidin-2-one		C₃₉H₄₆F₂N₂O₅Si₂	详情	详情
(X)	62212	(3R,4S)-1-(4-fluorophenyl)-3-{(3S)-3-(4-fluorophenyl)-3-[(trimethylsilyl)oxy]propyl}-4-{4-[(trimethylsilyl)oxy]phenyl}-2-azetidinone		C₃₀H₃₇F₂NO₃Si₂	详情	详情

Extended Information