【结 构 式】 |
【分子编号】50942 【品名】(S)-Benzyl 2-azetidinone-4-carboxylate; Benzyl (S)-4-oxo-2-azetidinecarboxylate 【CA登记号】72776-05-7 |
【 分 子 式 】C11H11NO3 【 分 子 量 】205.21328 【元素组成】C 64.38% H 5.4% N 6.83% O 23.39% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The homochiral azetidinone (IX) was prepared from the known beta-lactam (VIII) by N-silylation with tert-butyldimethylsilyl chloride followed by catalytic hydrogenolysis of the benzyl ester. The 3-silylated azetidinone intermediate (X) was obtained by treatment of the lithium enolate of (IX) with trimethylsilyl chloride. Subsequent Peterson reaction of (X) with the 4-silyloxybenzaldehyde (XI) and LDA furnished olefin (XII) as a mixture of geometric isomers. After esterification of the carboxylate group of (XII) with benzyl alcohol in the presence of EDC to yield (XIII), the catalytic hydrogenation of the olefin double bond of (XIII) gave rise to the cis-azetidinone (XIV). The N-tert-butyldimethylsilyl group of (XIV) was selectively removed by treatment with HF in acetonitrile to afford (XV). Acylation of the lactam N of (XV) with acid chloride (VII) in the presence of sodium hexamethyldisilazide provided (XVI). The remaining silyl group of (XVI) was finally removed by treatment with ammonium hydrogen difluoride in NMP-DMF.
【1】 Adlington, R.M.; Baldwin, J.E.; Becker, G.W.; et al.; Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen. J Med Chem 2001, 44, 10, 1491. |
【2】 Chen, B.; Adlington, R.M.; Baldwin, J.E.; et al.; Design and synthesis of novel monocyclic beta-lactam inhibitors of prostate specific antigen. Bioorg Med Chem Lett 1997, 7, 13, 1689. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XIIa) | 50935 | (2S)-1-[tert-butyl(dimethyl)silyl]-3-[(Z)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylic acid | C33H41NO4Si2 | 详情 | 详情 | |
(XIIb) | 50936 | (2S)-1-[tert-butyl(dimethyl)silyl]-3-[(E)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylic acid | C33H41NO4Si2 | 详情 | 详情 | |
(XIIIa) | 50937 | benzyl (2S)-1-[tert-butyl(dimethyl)silyl]-3-[(Z)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylate | C40H47NO4Si2 | 详情 | 详情 | |
(XIIIb) | 50938 | benzyl (2S)-1-[tert-butyl(dimethyl)silyl]-3-[(E)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylate | C40H47NO4Si2 | 详情 | 详情 | |
(VII) | 50932 | benzyl 3-(2-chloro-2-oxoethyl)benzoate | C16H13ClO3 | 详情 | 详情 | |
(VIII) | 50942 | (S)-Benzyl 2-azetidinone-4-carboxylate; Benzyl (S)-4-oxo-2-azetidinecarboxylate | 72776-05-7 | C11H11NO3 | 详情 | 详情 |
(IX) | 49426 | (2S)-1-[tert-butyl(dimethyl)silyl]-4-oxo-2-azetidinecarboxylic acid | C10H19NO3Si | 详情 | 详情 | |
(X) | 50933 | lithium (2R)-1-[tert-butyl(dimethyl)silyl]-4-oxo-3-(trimethylsilyl)-2-azetidinecarboxylate | C13H26LiNO3Si2 | 详情 | 详情 | |
(XI) | 50934 | 4-[[tert-butyl(diphenyl)silyl]oxy]benzaldehyde | C23H24O2Si | 详情 | 详情 | |
(XIV) | 50939 | benzyl (2S,3S)-1-[tert-butyl(dimethyl)silyl]-3-(4-[[tert-butyl(diphenyl)silyl]oxy]benzyl)-4-oxo-2-azetidinecarboxylate | C40H49NO4Si2 | 详情 | 详情 | |
(XV) | 50940 | benzyl (2S,3S)-3-(4-[[tert-butyl(diphenyl)silyl]oxy]benzyl)-4-oxo-2-azetidinecarboxylate | C34H35NO4Si | 详情 | 详情 | |
(XVI) | 50941 | benzyl (2S,3S)-1-(2-[3-[(benzyloxy)carbonyl]phenyl]acetyl)-3-(4-[[tert-butyl(diphenyl)silyl]oxy]benzyl)-4-oxo-2-azetidinecarboxylate | C50H47NO7Si | 详情 | 详情 |