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【结 构 式】 
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【分子编号】16800 【品名】(2R)-2-(4-chlorophenyl)oxirane 【CA登记号】 |
【 分 子 式 】C8H7ClO 【 分 子 量 】154.59568 【元素组成】C 62.15% H 4.56% Cl 22.93% O 10.35% |
合成路线1
该中间体在本合成路线中的序号：(VIb)2) The (R)- and (S)-enantiomers eliprodil are obtained as follows: The asymmetric dihydroxylation of 4-chlorostyrene (IV) by the Sharpless asymmetric dihydroxylation (AD) procedure (J Org Chem 1992, 57: 2768) methods alpha and beta (AD-alpha and AD-beta) gives both the (S)- and (R)-enantiomers of 1-(4-chlorophenyl)ethane-1,2-diol (Valpha) and (Vbeta), respectively. These compounds, by treatment first with methanesulfonyl chloride and then with K2CO3, yield the corresponding epoxides (VIalpha) and (VIbeta), respectively. Finally, both compounds are condensed with 4-(4-fluorobenzyl)piperidine (II) in refluxing isopropanol.
| 【1】 Di Fabio, R.; Thomas, R.J.; Pietra, C.; Ziviani, L.; The asymmetric synthesis of both enantiomers of eliprodil. Bioorg Med Chem Lett 1995, 5, 6, 551. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Va) | 16797 | (1S)-1-(4-chlorophenyl)-1,2-ethanediol | C8H9ClO2 | 详情 | 详情 | |
| (Vb) | 16798 | (1R)-1-(4-chlorophenyl)-1,2-ethanediol | C8H9ClO2 | 详情 | 详情 | |
| (VIa) | 16799 | (2S)-2-(4-chlorophenyl)oxirane | C8H7ClO | 详情 | 详情 | |
| (VIb) | 16800 | (2R)-2-(4-chlorophenyl)oxirane | C8H7ClO | 详情 | 详情 | |
| (S)-isomer | 16801 | (1S)-1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidino]-1-ethanol | C20H23ClFNO | 详情 | 详情 | |
| (R)-isomer | 16802 | (1R)-1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidino]-1-ethanol | C20H23ClFNO | 详情 | 详情 | |
| (II) | 16794 | 4-(4-fluorobenzyl)piperidine | 92822-02-1 | C12H16FN | 详情 | 详情 |
| (IV) | 16796 | p-chlorostyrene; 1-chloro-4-vinylbenzene | 1073-67-2 | C8H7Cl | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The enzymatic hydrolysis of (rac)-2-(4-chlorophenyl)oxirane (I) with Solanum tuberosum hydrolase enzyme (St-EH) gives a mixture of unreacted (R)-epoxide (R)-(II) and (R)-diol (R)-(III); this enzyme attacks with marked preference the (S)-epoxide at the more substituted position, with inversion of the configuration. The resulting mixture, without isolation, is treated with Aspergillus niger hydrolase enzyme (At-EH), affording enantiomerically pure (R)-diol (R)-(III); this enzyme attacks with marked preference the (R)-epoxide (R)-(II) at the less-substituted position, consequently with retention of the configuration. The resulting (R)-diol (R)-(III) is converted into (R)-(-)-212381 by known methods.
| 【1】 Manoj, K.M.; Baratti, J.; Archelas, A.; Furstoss, R.; Microbiological transformations. Part 45: A green chemistry preparative scale synthesis of enantiopure building blocks of eliprodil: Elaboration of a high substrate concentration epoxide hydrolase-catalyzed hydrolytic kinetic resolution process. Tetrahedron 2001, 57, 4, 695. |
| 【2】 Di Fabio, R.; Thomas, R.J.; Pietra, C.; Ziviani, L.; The asymmetric synthesis of both enantiomers of eliprodil. Bioorg Med Chem Lett 1995, 5, 6, 551. |