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【结 构 式】 
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【分子编号】17076 【品名】methyl (2S)-2-[(heptyloxy)methoxy]propanoate 【CA登记号】 |
【 分 子 式 】C12H24O4 【 分 子 量 】232.32016 【元素组成】C 62.04% H 10.41% O 27.55% |
合成路线1
该中间体在本合成路线中的序号：(XXIII)The bromosulfonate (XXI) has been obtained as follows: (S)-Lactic acid methyl ester (XXII) has been protected as its benzyloxymethyl ether (XXIII) according to Tetrahedron Lett 1980, 21: 1035. The reduction of (XXIII) with DIBAL yields the corresponding aldehyde (XXIV), which by a Grignard reaction with ethylmagnesium bromide in THF and chromatographic separation of the diastereoisomers (SiO2, hexane/ethyl acetate) affords 2(S)-(benzyloxymethoxy)-3(R)-pentanol (XXV). Finally, this compound is sulfonated to (XXI) with 4-bromobenzenesulfonyl chloride. Finally, compound (XX) is condensed with 2(S)-(benzyloxymethoxy)-3(R)-pentanol 4-bromobenzenesulfonate ester (XXI) by means of cesium carbonate in DMF, and deprotected with 6N HCl.
| 【1】 Fromtling, R.A.; Castañer, J.; SCH-56592. Drugs Fut 1996, 21, 2, 160. |
| 【2】 Saksena, A.K.; Girijavallabhan, V.M.; Lovey, R.G.; Pike, R.E.; Wang, H.; Liu, Y.-T.; Ganguly, A.K.; Bennett, F. (Schering Corp.); Tetrahydrofuran antifungals. EP 0736030; JP 1997500658; US 5661151; US 5703079; WO 9517407 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 18964 | 4-bromobenzenesulfonyl chloride | 98-58-8 | C6H4BrClO2S | 详情 | 详情 | |
| (XX) | 16351 | 4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C32H32F2N8O3 | 详情 | 详情 | |
| (XXI) | 17074 | (1R,2S)-1-ethyl-2-[(heptyloxy)methoxy]propyl 4-bromobenzenesulfonate | C19H31BrO5S | 详情 | 详情 | |
| (XXII) | 17075 | propionic acid, 2-hydroxy-, methyl ester, (S)-; methyl (2S)-2-hydroxypropanoate | 27871-49-4 | C4H8O3 | 详情 | 详情 |
| (XXIII) | 17076 | methyl (2S)-2-[(heptyloxy)methoxy]propanoate | C12H24O4 | 详情 | 详情 | |
| (XXIV) | 17077 | (2S)-2-[(heptyloxy)methoxy]propanal | C11H22O3 | 详情 | 详情 | |
| (XXV) | 17078 | (2S,3R)-2-[(heptyloxy)methoxy]-3-pentanol | C13H28O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)
| 【1】 Bennett F, Sakasena AK, Lovey R, et al. 2006. Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048, and the discovery of posaconazole(Sch 56592) . Bioorg Med Chem Lett, 16, 186～190 |
| 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) | 17075 | propionic acid, 2-hydroxy-, methyl ester, (S)-; methyl (2S)-2-hydroxypropanoate | 27871-49-4 | C4H8O3 | 详情 | 详情 |
| (II) | 17076 | methyl (2S)-2-[(heptyloxy)methoxy]propanoate | C12H24O4 | 详情 | 详情 | |
| (III) | 17077 | (2S)-2-[(heptyloxy)methoxy]propanal | C11H22O3 | 详情 | 详情 | |
| (IV) | 17078 | (2S,3R)-2-[(heptyloxy)methoxy]-3-pentanol | C13H28O3 | 详情 | 详情 | |
| (V) | 17074 | (1R,2S)-1-ethyl-2-[(heptyloxy)methoxy]propyl 4-bromobenzenesulfonate | C19H31BrO5S | 详情 | 详情 | |
| (VI) | 16351 | 4-[4-[4-(4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methoxy]phenyl)-1-piperazinyl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C32H32F2N8O3 | 详情 | 详情 |