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【结 构 式】 
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【分子编号】38532 【品名】methyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate 【CA登记号】122743-18-4 |
【 分 子 式 】C10H12O4 【 分 子 量 】196.20288 【元素组成】C 61.22% H 6.16% O 32.62% |
合成路线1
该中间体在本合成路线中的序号：(II)The asymmetric dihydroxylation of methyl cinnamate (I) with AD-alpha reagent in tert-butanol/water gives the (2R,3S)-dihydroxyester (II), which is treated with trimethyl orthobenzoate (III) and TsOH in dichloromethane yielding the benzoate (IV). This compound, without isolation, is treated with acetyl bromide affording (2S,3R)-2-(benzoyloxy)-3-bromo-3-phenylpropionic acid methyl ester (V), which is treated with sodium azide in DMF to give the corresponding (2R,3S)-azido compound (VI). Finally, this compound is reduced with H2 over Pd/C in methanol to the corresponding amine that suffers a benzoyl transposition yielding the target side chain (VII).
| 【1】 Hu, Z.; et al.; Utilization of a benzoyl migration to effect an expeditious synthesis of the paclitaxel C-13 side chain. Org Process Res Dev 1997, 1, 5, 387. |
| 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) | 23888 | methyl (E)-3-phenyl-2-propenoate | 103-26-4 | C10H10O2 | 详情 | 详情 |
| (II) | 38532 | methyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate | 122743-18-4 | C10H12O4 | 详情 | 详情 |
| (III) | 38531 | dimethoxy(phenyl)methyl methyl ether; 1-(trimethoxymethyl)benzene | 707-07-3 | C10H14O3 | 详情 | 详情 |
| (IV) | 38533 | (1R,2S)-2-hydroxy-1-(methoxycarbonyl)-2-phenylethyl benzoate | C17H16O5 | 详情 | 详情 | |
| (V) | 38534 | (1S,2R)-2-bromo-1-(methoxycarbonyl)-2-phenylethyl benzoate | C17H15BrO4 | 详情 | 详情 | |
| (VI) | 38535 | (1R,2S)-2-azido-1-(methoxycarbonyl)-2-phenylethyl benzoate | C17H15N3O4 | 详情 | 详情 | |
| (VII) | 63559 | methyl (2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoate | 32981-85-4 | C17H17NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)2(R),3(S)-Dihydroxy-3-phenylpropionic acid methyl ester, an intermediate in the paclitaxel side chain synthesis, can be prepared by the Sharpless catalytic asymmetric dihydroxylation of methyl cinnamate (I) with K2OsO4, N-methylmorpholine N-oxide (NMO) and a catalytic amount of 1,4-bis(9-O-dihydroquinine)phthalazine [(DHQ)2PHAL] in tert-butanol/water. This reaction has been tested successfully in a 50-kg industrial process.
| 【1】 Lu, X.; et al.; Process development of the sharpless catalytic asymmetric dihydroxylation reaction to prepare methyl (2R,3S)-2,3-dihydroxy-3-phenylpropionate. Org Process Res Dev 2000, 4, 6, 575. |