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【结 构 式】

【分子编号】30647

【品名】benzyl (2S,3S)-2-methyl-4-oxoazetidinylcarbamate

【CA登记号】

【 分 子 式 】C12H14N2O3

【 分 子 量 】234.25484

【元素组成】C 61.53% H 6.02% N 11.96% O 20.49%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

The reaction of N-tert-butoxycarbonylthreonin (I) with O-benzylhydroxylamine (II) by means of N-hydroxybenzotriazole acid dicyclohexylcarbodiimide in THF gives N-tert-butoxycarbonyl-N-benzyloxythreoninamide (III), which is cyclized by means of triphenylphosphine and diethyl azodicarboxylate in THF yielding N-benzyloxy-3-(tert-butoxycarbonylamino)-4-methylazetidin-2-one (IV). The hydrogenolysis of (IV) with H2 over Pd/C in ethanol affords 3-(tert-butoxycarbonylamino)-4-methyl-N-hydroxyazetidin-2-one (V), which is reduced with TiCl3 in ethanol - aqueous ammnonium acetate giving 3-(tert-butoxycarbonylamino)-4-methylazetidin-2-one (VI). The hydrolysis of (VI) with trifluoroacetic acid in CH2Cl2 anisole, followed by reaction with benzyl chloroformate in acetone yields 3-(benzyloxycarbonylamino)-4-methylazetidin-2-one (VII). The sulfonation of (VII) with SO3 in DMF, and treatment of the resulting product with tetrabutylammonium sulfate in CH2Cl2 affords 3-(benzyloxycarbonylamino)-4-methyl-2-oxoazetidin-1-sulfonic acid tetrabutylammonium salt (VIII), which is debenzylated by hydrogenolysis with H2 over Pd/C in DMF giving 3-amino-4-methyl-2-oxoazetidin-1-sulfonic acid tetrabutylammonium salt (IX). The condensation of (IX) with alpha-[[(1-diphenylmethoxycarbonyl)-1-methylethoxy]imino]-(2-amino-4-thiazolyl)acetic acid (X), by means of N-hydroxybenzotriazole or N-hydroxysuccinimide and dicyclohexylcarbodiimide in acetone yields 3-[[(2-amino-4-thiazolyl)[[1-(diphenylmethoxycarbonyl]-1-methylethoxy]imino]acetyl]amino]-4-methyl-2-oxoazetidine-1-sulfonic acid (XI), which is finally hydrolyzed with trifluoroacetic acid.

1 Fox, R.; Denzel, T.W.; Singh, J.; et al.; Regioselective activation of aminothiazole(iminoxyacetic acid)acetic acid: An efficient synthesis of the monobactam aztreonam. Org Process Res Dev 2002, 6, 6, 863.
2 Sykes, R.B.; Parker, W.L.; Cimarusti, C.M.; Koster, W.H.; Slusarchyk, W.A.; Fritz, A.W.; Floyd, D.M. (Bristol-Myers Squibb Co.); beta-Lactam antibiotics containing sulphonic groups. BE 0887428; DE 3104145; GB 2071650; JP 56125362 .
3 Castaner, J.; Blancafort, P.; Serradell, M.N.; Aztreonam. Drugs Fut 1983, 8, 4, 295.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(I) 30642 (2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxybutyric acid 2592-18-9 C9H17NO5 详情 详情
(II) 14640 O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene 622-33-3 C7H9NO 详情 详情
(III) 30643 tert-butyl (1S,2S)-1-[[(benzyloxy)amino]carbonyl]-2-hydroxypropylcarbamate C16H24N2O5 详情 详情
(IV) 30644 tert-butyl (2S,3S)-1-(benzyloxy)-2-methyl-4-oxoazetidinylcarbamate C16H22N2O4 详情 详情
(V) 30645 tert-butyl (2S,3S)-1-hydroxy-2-methyl-4-oxoazetidinylcarbamate C9H16N2O4 详情 详情
(VI) 30646 tert-butyl (2S,3S)-2-methyl-4-oxoazetidinylcarbamate C9H16N2O3 详情 详情
(VII) 30647 benzyl (2S,3S)-2-methyl-4-oxoazetidinylcarbamate C12H14N2O3 详情 详情
(VIII) 30648 N,N,N-tributyl-1-butanaminium (2S,3S)-3-[[(benzyloxy)carbonyl]amino]-2-methyl-4-oxo-1-azetidinesulfonate C28H49N3O6S 详情 详情
(IX) 30649 N,N,N-tributyl-1-butanaminium (2S,3S)-3-amino-2-methyl-4-oxo-1-azetidinesulfonate C20H43N3O4S 详情 详情
(X) 30650 2-(2-amino-1,3-thiazol-4-yl)-2-[[2-(benzhydryloxy)-1,1-dimethyl-2-oxoethoxy]imino]acetic acid C22H21N3O5S 详情 详情
(XI) 30651 (2S,3S)-3-[(2-(2-amino-1,3-thiazol-4-yl)-2-[[2-(benzhydryloxy)-1,1-dimethyl-2-oxoethoxy]imino]acetyl)amino]-2-methyl-4-oxo-1-azetidinesulfonic acid C26H27N5O8S2 详情 详情
Extended Information