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【结 构 式】 
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【分子编号】62212 【品名】(3R,4S)-1-(4-fluorophenyl)-3-{(3S)-3-(4-fluorophenyl)-3-[(trimethylsilyl)oxy]propyl}-4-{4-[(trimethylsilyl)oxy]phenyl}-2-azetidinone 【CA登记号】 |
【 分 子 式 】C30H37F2NO3Si2 【 分 子 量 】553.7965264 【元素组成】C 65.07% H 6.73% F 6.86% N 2.53% O 8.67% Si 10.14% |
合成路线1
该中间体在本合成路线中的序号：(X)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 |