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【结 构 式】

【分子编号】50743

【品名】(2R)-2-(2,4-difluorophenyl)-2,3-dihydroxypropyl 2-methylpropanoate

【CA登记号】

【 分 子 式 】C13H16F2O4

【 分 子 量 】274.2644464

【元素组成】C 56.93% H 5.88% F 13.85% O 23.33%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXIV)

The intermediate (XIX) can be obtained by two related ways: 1. The condensation of 1,3-dichloroacetone (XIII) with 2,4-difluorobromobenzene (XII) by means of n-BuLi gives 1,3-dichloro-2-(2,4-difluorophenyl)-2-propanol (XIV), which is converted into the epoxide (XV) by reaction with KOH in toluene. The reaction of (XV) with isobutyric anhydride (XXII) yields the diester (XX), which is stereoselectively hydrolyzed with Lipase D in an acetate buffer to afford the (R)-monoester (XXIV). The reaction of (XXIV) with Ms-Cl and pyridine provides the monomesylate (XXV), which is treated with KOH in toluene to give the hydroxymethyl epoxide (XVII). Finally, this compound is treated with 1,2,4-triazole (XVIII) and K2CO3 in refluxing THF to afford the target intermediate. Alternatively, the mesylate (XXV) can be treated with 1,2,4-triazole (XVIII) and Na2CO3 in refluxing methanol to yield directly the target intermediate (XIX). 2. The acylation of 1,3-dihydroxypropanone (XXI) with butyric anhydride (XXII), pyridine and DMAP gives the diester (XXIII), which is submitted to a Grignard condensation with 2,4-difluorobromobenzene (XIII) by means of Mg to afford the already described intermediate, the diester (XIX).

1 Yasohara, Y.; et al.; A practical chemoenzymatic synthesis of a key intermediate of antifungal agents. Tetrahedron Lett 2001, 42, 19, 3331.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XII) 63907 1,3-dichloroacetone C3H4Cl2O 详情 详情
(XIII) 15488 1-bromo-2,4-difluorobenzene 348-57-2 C6H3BrF2 详情 详情
(XIV) 15489 1,3-dichloro-2-(2,4-difluorophenyl)-2-propanol C9H8Cl2F2O 详情 详情
(XV) 15490 2-(chloromethyl)-2-(2,4-difluorophenyl)oxirane C9H7ClF2O 详情 详情
(XVII) 17058 [(2S)-2-(2,4-difluorophenyl)oxiranyl]methanol C9H8F2O2 详情 详情
(XVIII) 13135 1H-1,2,4-Triazole; 1,2,4-Triazole 288-88-0 C2H3N3 详情 详情
(XIX) 15494 (2S)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)-1,2-propanediol C11H11F2N3O2 详情 详情
(XX) 50741 2-(2,4-difluorophenyl)-2-hydroxy-3-(isobutyryloxy)propyl 2-methylpropanoate C17H22F2O5 详情 详情
(XXI) 14575 Dihydroxyacetone; 1,3-dihydroxyacetone 96-26-4 C3H6O3 详情 详情
(XXII) 22334 1-methylpropionic anhydride 97-72-3 C8H14O3 详情 详情
(XXIII) 50742 3-(isobutyryloxy)-2-oxopropyl 2-methylpropanoate C11H18O5 详情 详情
(XXIV) 50743 (2R)-2-(2,4-difluorophenyl)-2,3-dihydroxypropyl 2-methylpropanoate C13H16F2O4 详情 详情
(XXV) 50744 (2S)-2-(2,4-difluorophenyl)-2-hydroxy-3-[(methylsulfonyl)oxy]propyl 2-methylpropanoate C14H18F2O6S 详情 详情
Extended Information