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【结 构 式】 
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【分子编号】53624 【品名】4-[(3,3-diethyl-4-oxo-2-azetidinyl)oxy]benzoic acid 【CA登记号】n/a |
【 分 子 式 】C14H17NO4 【 分 子 量 】263.29332 【元素组成】C 63.87% H 6.51% N 5.32% O 24.31% |
合成路线1
该中间体在本合成路线中的序号：(VII)In a different procedure, displacement of the propionate group of azetidinone (IV) by benzyl 4-hydroxybenzoate (V) in the presence of Cs2CO3 afforded the racemic adduct (VI). Subsequent transfer hydrogenolysis of (VI) with cyclohexene and Pd/C provided the carboxylic acid (VII), which was resolved employing (S)-alpha-methylbenzylamine. Alternatively, a kinetic enzymatic resolution of the benzyl ester (VI) was developed. Treatment of ester (VI) with lipase PS-800 provided the desired (S)-acid (VIII), while leaving the unchanged (R)-benzyl ester. Coupling of acid (VIII) with N-methylpiperazine (III) in the presence of DCC and HOBt furnished the corresponding amide (IX).
| 【1】 Cvetovich, R.J.; et al.; An asymmetric synthesis of L-694,458, a human leukocyte elastase inhibitor, via novel enzyme resolution of beta-lactam esters. J Org Chem 1996, 61, 19, 6575. |
| 【2】 Li, H.-Y.; Fortunak, J.M.; Storace, L.; Sheeran, P.J.; Anzalone, L. (DuPont Pharmaceuticals Co.); An efficient process for the preparation of a human leukocyte elastase inhibitor. WO 0012474 . |
| 【3】 Amato, J.S.; Cvetovich, R.; Hartner, F.W. (Merck & Co., Inc.); Process for preparing substd. azetidinones. WO 9716448 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (IV) | 53621 | 3,3-diethyl-4-oxo-2-azetidinyl propionate | n/a | C10H17NO3 | 详情 | 详情 |
| (V) | 53622 | 4-Hydroxybenzoic acid benzyl ester; Benzyl 4-hydroxybenzoate; Benzyl-p-Hydroxybenzoate; Benzylparaben | 94-18-8 | C14H12O3 | 详情 | 详情 |
| (VI) | 53623 | benzyl 4-[(3,3-diethyl-4-oxo-2-azetidinyl)oxy]benzoate | n/a | C21H23NO4 | 详情 | 详情 |
| (VII) | 53624 | 4-[(3,3-diethyl-4-oxo-2-azetidinyl)oxy]benzoic acid | n/a | C14H17NO4 | 详情 | 详情 |
| (VIII) | 53625 | 4-{[(2S)-3,3-diethyl-4-oxoazetidinyl]oxy}benzoic acid | n/a | C14H17NO4 | 详情 | 详情 |
| (IX) | 53626 | (4S)-3,3-diethyl-4-{4-[(4-methyl-1-piperazinyl)carbonyl]phenoxy}-2-azetidinone | n/a | C19H27N3O3 | 详情 | 详情 |