【结 构 式】 |
【分子编号】60185 【品名】ethyl methyliminoformate 【CA登记号】 |
【 分 子 式 】C4H9NO 【 分 子 量 】87.1216 【元素组成】C 55.15% H 10.41% N 16.08% O 18.36% |
合成路线1
该中间体在本合成路线中的序号:(B)Dynamic kinetic resolution of 3-acetyl-1-benzyl-2-pyrrolidinone (I) by Ru-BINAP catalyzed hydrogenation provides the (hydroxyethyl) pyrrolidinone (II). Subsequent reduction of lactam (II) employing NaBH4-BF3•Et2O affords pyrrolidine (III). After debenzylation of (III) by hydrogenation over Pd/C, the resultant pyrrolidine (IV) is protected as the corresponding N-Alloc derivative (V) upon treatment with allyl chloroformate. Subsequent Swern oxidation of the alcohol function of (V) leads to the optically pure ketone (VI). Treatment of ketone (VI) with Me3SiOTf and Et3N, followed by condensation with the acetoxyazetidinone (VII) affords adduct (VIII). Acylation of azetidinone (VIII) with allyl oxalyl chloride (IX), followed by cyclization of the intermediate oxalimide in the presence of triethyl phosphite, gives rise to the carbapenem system ( X). Desilylation of (X) with tetrabutylammonium fluoride leads to alcohol (XI). Further palladium-catalyzed deprotection of both the Alloc and allyl ester groups of (XI) provides the pyrrolidinyl carbapenem (XII). Finally, introduction of the desired N-methyl formimidoyl group into (XII) is accomplished by treatment with ethyl N-methyl formimidate.
【1】 Hattori, K.; et al.; Synthesis and antibacterial evaluation of novel 2-[N-imidoylpyrrolidinyl] carbapenems. Bioorg Med Chem Lett 2002, 12, 3, 383. |
【2】 Murata, M.; Chiba, T.; Tsutsumi, H.; Hattori, K.; Kuroda, S.; Ohtake, H.; Shirai, F. (Fujisawa Pharmaceutical Co., Ltd.); 1-Azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid cpds.. EP 0394991; JP 1990300187; US 5102877 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 38115 | 3-[(chlorocarbonyl)oxy]-1-propene | 2937-50-0 | C4H5ClO2 | 详情 | 详情 |
(B) | 60185 | ethyl methyliminoformate | C4H9NO | 详情 | 详情 | |
(I) | 60175 | 3-acetyl-1-benzyl-2-pyrrolidinone | C13H15NO2 | 详情 | 详情 | |
(II) | 60176 | (3S)-1-benzyl-3-[(1R)-1-hydroxyethyl]-2-pyrrolidinone | C13H17NO2 | 详情 | 详情 | |
(III) | 60177 | (1R)-1-[(3R)-1-benzylpyrrolidinyl]-1-ethanol | C13H19NO | 详情 | 详情 | |
(IV) | 60178 | (1R)-1-[(3R)pyrrolidinyl]-1-ethanol | C6H13NO | 详情 | 详情 | |
(V) | 60179 | allyl (3R)-3-[(1R)-1-hydroxyethyl]-1-pyrrolidinecarboxylate | C10H17NO3 | 详情 | 详情 | |
(VI) | 60180 | allyl (3R)-3-acetyl-1-pyrrolidinecarboxylate | C10H15NO3 | 详情 | 详情 | |
(VII) | 11687 | (2R,3R)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetanyl acetate | C13H25NO4Si | 详情 | 详情 | |
(VIII) | 60181 | allyl (3R)-3-{2-[(2R,3S)-3-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-oxoazetidinyl]acetyl}-1-pyrrolidinecarboxylate | C21H36N2O5Si | 详情 | 详情 | |
(IX) | 15585 | allyl 2-chloro-2-oxoacetate | C5H5ClO3 | 详情 | 详情 | |
(X) | 60182 | 2-propenyl 6-(1-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-7-oxo-3-{1-[(2-propenyloxy)carbonyl]-3-pyrrolidinyl}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C26H40N2O6Si | 详情 | 详情 | |
(XI) | 60183 | 2-propenyl 6-(1-hydroxyethyl)-7-oxo-3-{1-[(2-propenyloxy)carbonyl]-3-pyrrolidinyl}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C20H26N2O6 | 详情 | 详情 | |
(XII) | 60184 | 6-(1-hydroxyethyl)-7-oxo-3-(3-pyrrolidinyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid | C13H18N2O4 | 详情 | 详情 |