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【结 构 式】

【分子编号】53476

【品名】1-(4-fluorophenyl)-5-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-1,5-pentanedione

【CA登记号】n/a

【 分 子 式 】C20H18FNO4

【 分 子 量 】355.3656632

【元素组成】C 67.6% H 5.11% F 5.35% N 3.94% O 18.01%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(I)

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.

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:(I)

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.

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:(V)

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

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