【结 构 式】 |
【分子编号】22571 【品名】3-[(4-nitrobenzyl)oxy]-3-oxopropanoate 【CA登记号】 |
【 分 子 式 】C10H8MgNO6 【 分 子 量 】262.48166 【元素组成】C 45.76% H 3.07% Mg 9.26% N 5.34% O 36.57% |
合成路线1
该中间体在本合成路线中的序号:(VI)The condensation of (3R,4R)-4-acetoxy-3-[1(R)-(tert-butyldimethylsilylioxy)ethyl)azetidin-2-one (I) with benzyl 2-bromopropionate (II) by means of diethylaluminum chloride in hexane - THF gives the isomeric mixture (III), (IIIa), which is separated by column chrornatography and the correct isomer (III) is treated with tert-butyldimethylsilyl chloride to yield the silylated azetidine (IV). The reductive debenzylation of (IV) with H2 over Pd/C in methanol affords the protected free acid (V), which is condensed with magnesium 4-nitrobenzylmalonate (VI) by means of carbonyldiimidazole (CDI) in hot acetonitrile to give the protected ketoester (VII). Partial hydrolysis of (VII) with HCl in methanol affords the free ketoester (VIII), which is treated with p-toluenesulfonylazide in acetonitrile yielding the diazo compound (IX). The cyclization of (IX) by means of rhodium acetate in refluxing toluene gives 6alpha-[1(R)-hydroxyethyl)-1beta-methyl-2-oxo-1-dethia-1-carba-2-penem-3-car boxylic acid 4-nitrobenzyl ester (X), which is condensed with diphenyl chlorophosphate (XI) by means of diisopropylethylamine in acetonitrile, yielding the enol ester (XII).
【1】 Fukasawa, M.; Inoue, T.; Kato, M.; Matsumura, H.; Sunagawa, M. (Sumitomo Pharmaceuticals Co., Ltd.); Thiopyrrolidinyl-beta-lactam derivs.. EP 0126587; ES 8600305; JP 1985001186; JP 1985019787; JP 1991041066; US 4933333; US 4943569; US 5122604 . |
【2】 Prous, J.; Castaner, J.; SM-7338. Drugs Fut 1988, 13, 6, 534. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IIIa) | 22568 | benzyl (2S)-2-[(2S,3S)-3-(1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetidinyl]propanoate | C21H33NO4Si | 详情 | 详情 | |
(I) | 22565 | methyl (2S,3S)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxo-2-azetidinecarboxylate | C13H25NO4Si | 详情 | 详情 | |
(II) | 16074 | Diphenyl phosphoryl chloride; 1,1'-Diphenylphosphoryl chloride; Chlorodiphenyl Phosphate; Diphenyl chlorophosphate; Diphenylchlorophosphate | 2524-64-3 | C12H10ClO3P | 详情 | 详情 |
(II) | 22566 | benzyl 2-bromopropanoate | 3017-53-6 | C10H11BrO2 | 详情 | 详情 |
(III) | 22567 | benzyl 2-[(2S,3S)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetidinyl]propanoate | C21H33NO4Si | 详情 | 详情 | |
(IV) | 22569 | benzyl 2-[(2S,3S)-1-[tert-butyl(dimethyl)silyl]-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetidinyl]propanoate | C27H47NO4Si2 | 详情 | 详情 | |
(V) | 22570 | 2-[(2S,3S)-1-[tert-butyl(dimethyl)silyl]-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetidinyl]propionic acid | C20H41NO4Si2 | 详情 | 详情 | |
(VI) | 22571 | 3-[(4-nitrobenzyl)oxy]-3-oxopropanoate | C10H8MgNO6 | 详情 | 详情 | |
(VII) | 22572 | 4-nitrobenzyl 4-[(2R,3S)-1-[tert-butyl(dimethyl)silyl]-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetidinyl]-3-oxopentanoate | C29H48N2O7Si2 | 详情 | 详情 | |
(VIII) | 22573 | 4-nitrobenzyl 4-[(2R,3S)-3-[(1R)-1-hydroxyethyl]-4-oxoazetidinyl]-3-oxopentanoate | C17H20N2O7 | 详情 | 详情 | |
(IX) | 30150 | (3S,4R)-3-((1R)-1-Hydroxyethyl)-4[(1R)-1-methyl-3-diazo-3-(p-nitrobenzyloxycarbonyl)-2-oxopropyl]azetidin-2-one | 137391-68-5 | C17H18N4O7 | 详情 | 详情 |
(X) | 22575 | 4-nitrobenzyl (2R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate | C17H18N2O7 | 详情 | 详情 | |
(XII) | 22577 | 4-nitrobenzyl (5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C29H27N2O10P | 详情 | 详情 |