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【结 构 式】 
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【分子编号】38579 【品名】2-[[2-methyl-1-(propionyloxy)propoxy](4-phenylbutyl)phosphoryl]acetic acid 【CA登记号】 |
【 分 子 式 】C19H29O6P 【 分 子 量 】384.409422 【元素组成】C 59.37% H 7.6% O 24.97% P 8.06% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)The reaction of 4-phenyl-1-butene (XX) with hypophosphorous acid gives 4-phenylbutylphosphinic acid (XXI), which is condensed with chloroacetic acid (XXII) yielding 2-[hydroxy(4-phenylbutyl)phosphoryl]acetic acid (XXIII). The esterifica-tion of (XXII) with benzyl alcohol affords the benzyl acetate (XXIV), which is esterified at the OH group of the phosphinic acid with 2-methyl-1-(propionyloxy)propyl chloride (XXV) giving the completely esterified derivative (XXVI). The debenzylation of (XXVI) with H2 over Pd/C yields the acetic acid derivative (XXVII), which is submitted to optical resolution affording the desired (S)-isomer (XXVIII). Finally, this compound is condensed with the desired intermediate trans-4-cyclohexyl-L-proline (XI) by means of CDI and NaOH.
| 【1】 Anderson, N.G.; et al.; Generation and fate of regioisomeric side-chain impurities in the preparation of fosinopril sodium. Org Process Res Dev 1997, 1, 4, 315. |
| 【2】 Anderson, N.G.; et al.; Process development for the preparation of a monopril intermediate by a trimethylsilyl-modified arbuzov reaction. Org Process Res Dev 1997, 1, 3, 211. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 38567 | (2S,4S)-4-cyclohexyl-2-pyrrolidinecarboxylic acid | C11H19NO2 | 详情 | 详情 | |
| (XX) | 20933 | 1-(3-butenyl)benzene | 768-56-9 | C10H12 | 详情 | 详情 |
| (XXI) | 20932 | 4-phenylbutylphosphinic acid | C10H15O2P | 详情 | 详情 | |
| (XXII) | 11847 | 2-Chloroacetic acid; Chloroacetic Acid | 79-11-8 | C2H3ClO2 | 详情 | 详情 |
| (XXIII) | 38575 | 2-[hydroxy(4-phenylbutyl)phosphoryl]acetic acid | C12H17O4P | 详情 | 详情 | |
| (XXIV) | 38576 | 2-(benzyloxy)-2-oxoethyl(4-phenylbutyl)phosphinic acid | C19H23O4P | 详情 | 详情 | |
| (XXV) | 38577 | 1-chloro-2-methylpropyl propionate | C7H13ClO2 | 详情 | 详情 | |
| (XXVI) | 38578 | 1-[[[2-(benzyloxy)-2-oxoethyl](4-phenylbutyl)phosphoryl]oxy]-2-methylpropyl propionate | C26H35O6P | 详情 | 详情 | |
| (XXVII) | 38579 | 2-[[2-methyl-1-(propionyloxy)propoxy](4-phenylbutyl)phosphoryl]acetic acid | C19H29O6P | 详情 | 详情 | |
| (XXVIII) | 38580 | 2-[[[(1S)-2-methyl-1-(propionyloxy)propyl]oxy](4-phenylbutyl)phosphoryl]acetic acid | C19H29O6P | 详情 | 详情 |