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【结 构 式】 
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【分子编号】16298 【品名】4-oxo-2-azetanyl benzoate; 4-Benzoyloxy-2-azetidinone 【CA登记号】28562-58-5 |
【 分 子 式 】C10H9NO3 【 分 子 量 】191.1864 【元素组成】C 62.82% H 4.74% N 7.33% O 25.11% |
合成路线1
该中间体在本合成路线中的序号：(IV)The ethyl ester (III), a chiral key intermediate of this synthesis, can be obtained as follows: 1) The reaction of 4-(benzoyloxy)-2-azetidinone (IV) with 2 equivalents of 1-lithio-2-(trimethylsilyl)acetylene (V) gives azetidinone (VI), which is opened with anhydrous HCl in ethanol, yielding racemic 3-amino-5-(trimethylsilyl)-4-pentynoic acid ethyl ester (VII). Resolution of (VII) by means of diastereomeric amide formation with (R)-O-methyl mandelic acid chloride (VIII) and chromatographic separation of the diastereoisomers (MPLC, ether/hexane) affords the amide (IX), which is then N-protected with Boc2O in acetonitrile to give (X). Treatment of (X) with tetramethylguanidine in methanol gives methyl ester (XI), which is finally treated first with TFA and then with HCl in ethanol to afford ethyl ester (III).
| 【1】 Zablocki, J.A.; Rico, J.G.; Garland, R.B.; et al.; Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg-Gly-Asp sequence of fibrinogen. (Aminobenzamidino)succinyl (ABAS) series of orally active fibrinogen receptor antagonists. J Med Chem 1995, 38, 13, 2378-94. |
| 【2】 Graul, A.; Martel, A.M.; Castaner, J.; Xemilofiban. Drugs Fut 1997, 22, 5, 508. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17739 | N,N,N',N'-tetramethylguanidine; 1,1,3,3-Tetramethylguanidine | 80-70-6 | C5H13N3 | 详情 | 详情 | |
| (III) | 16297 | ethyl (3S)-3-amino-4-pentynoate | C7H11NO2 | 详情 | 详情 | |
| (IV) | 16298 | 4-oxo-2-azetanyl benzoate; 4-Benzoyloxy-2-azetidinone | 28562-58-5 | C10H9NO3 | 详情 | 详情 |
| (V) | 16299 | Lithium (trimethylsilyl)acetylide; [2-(Trimethylsilyl)ethynyl]lithium | 54655-07-1 | C5H9LiSi | 详情 | 详情 |
| (VI) | 16300 | 4-[2-(trimethylsilyl)ethynyl]-2-azetanone | C8H13NOSi | 详情 | 详情 | |
| (VII) | 16301 | 3-amino-5-(trimethylsilyl)-4-pentynoic acid | C8H15NO2Si | 详情 | 详情 | |
| (VIII) | 16302 | (2R)-2-methoxy-2-phenylethanoyl chloride | C9H9ClO2 | 详情 | 详情 | |
| (IX) | 16303 | (3S)-3-[[(2R)-2-methoxy-2-phenylethanoyl]amino]-5-(trimethylsilyl)-4-pentynoic acid | C17H23NO4Si | 详情 | 详情 | |
| (X) | 16304 | ethyl (3S)-3-[(tert-butoxycarbonyl)[(2R)-2-methoxy-2-phenylethanoyl]amino]-5-(trimethylsilyl)-4-pentynoate | C24H35NO6Si | 详情 | 详情 | |
| (XI) | 17740 | ethyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-pentynoate | C12H19NO4 | 详情 | 详情 |