【结 构 式】 |
【分子编号】56419 【品名】benzhydryl 4-{[(2S,3S)-3-(2-ethoxybenzyl)-4-oxoazetidinyl]oxy}benzoate 【CA登记号】 |
【 分 子 式 】C32H29NO5 【 分 子 量 】507.586 【元素组成】C 75.72% H 5.76% N 2.76% O 15.76% |
合成路线1
该中间体在本合成路线中的序号:(VII)Alkylation of the dianion of azetidinonecarboxylic acid (I) with 2-ethoxybenzyl bromide (II) in cold THF affords (III). Oxidative cleavage of the carboxyl group of (III) using lead tetraacetate and HOAc provides the acetate ester (IV), which is desilylated to (V) with tetrabutylammonium fluoride in THF. Azetidinone (V) is coupled with benzhydryl 4-hydroxybenzoate (VI) to yield ether (VII). Curtius rearrangement of carboxylic acid (VIII) provides isocyanate (IX). Coupling between isocyanate (IX) and azetidine (VII) gives rise to urea (X). The benzhydryl ester group of (X) is finally cleaved by treatment with trifluoroacetic acid in the presence of anisole.
【1】 Nakajima, M.; Kii, M.; Uenaka, M. (Shionogi & Co. Ltd.); Monocyclic beta-lactam cpds. and chymase inhibitors containing the same. EP 1099690; WO 0005204 . |
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) | 28418 | (2R)-1-[tert-butyl(dimethyl)silyl]-4-oxo-2-azetidinecarboxylic acid | C10H19NO3Si | 详情 | 详情 | |
(II) | 56414 | 2-(bromomethyl)phenyl ethyl ether; 1-(bromomethyl)-2-ethoxybenzene | C9H11BrO | 详情 | 详情 | |
(III) | 56415 | (2R,3S)-1-[tert-butyl(dimethyl)silyl]-3-(2-ethoxybenzyl)-4-oxo-2-azetidinecarboxylic acid | C19H29NO4Si | 详情 | 详情 | |
(IV) | 56416 | (2S,3S)-1-[tert-butyl(dimethyl)silyl]-3-(2-ethoxybenzyl)-4-oxoazetidinyl acetate | C20H31NO4Si | 详情 | 详情 | |
(V) | 56417 | (2S,3S)-3-(2-ethoxybenzyl)-4-oxoazetidinyl acetate | C14H17NO4 | 详情 | 详情 | |
(VI) | 56418 | benzhydryl 4-hydroxybenzoate | C20H16O3 | 详情 | 详情 | |
(VII) | 56419 | benzhydryl 4-{[(2S,3S)-3-(2-ethoxybenzyl)-4-oxoazetidinyl]oxy}benzoate | C32H29NO5 | 详情 | 详情 | |
(VIII) | 43492 | 2-chloro-4-fluorobenzonitrile | 60702-69-4 | C7H3ClFN | 详情 | 详情 |
(IX) | 56420 | 1-[isocyanato(4-methylphenyl)methyl]-4-methylbenzene; bis(4-methylphenyl)methyl isocyanate | C16H15NO | 详情 | 详情 | |
(X) | 56421 | benzhydryl 4-{[(2S,3S)-1-({[bis(4-methylphenyl)methyl]amino}carbonyl)-3-(2-ethoxybenzyl)-4-oxoazetidinyl]oxy}benzoate | C48H44N2O6 | 详情 | 详情 |