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【结 构 式】 
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【分子编号】17094 【品名】(4R)-3-[(2S)-4-(2,4-difluorophenyl)-2-(hydroxymethyl)-4-pentenoyl]-4-heptyl-1,3-oxazolan-2-one 【CA登记号】 |
【 分 子 式 】C22H29F2NO4 【 分 子 量 】409.4734064 【元素组成】C 64.53% H 7.14% F 9.28% N 3.42% O 15.63% |
合成路线1
该中间体在本合成路线中的序号：(XLI)3) The Friedel Crafts condensation of m-difluorobenzene (XXXIV) with succinic anhydride (XXXV) gives 4-(2,4-difluorophenyl)-4-oxobutyric acid (XXXVI), which is converted by a Wittig reaction into 4-(2,4-difluorophenyl)-4-pentenoic acid (XXXVII) and subsequently into its acyl chloride (XXXVIII). The condensation of (XXXVIII) with 4(R)-benzyloxazolidin-2-one (XXXIX) gives the acyl oxazolidinone (XL), which is regioselectively hydroxymethylated with 1,3,5-trioxane and TiCl4 to afford 4(R)-benzyl-3-[4-(2,4-difluorophenyl)-3(S)-(hydroxymethyl)-4-pentenoyl] oxazolidin-2-one (XLI). The cyclization of (XLI) with iodine and pyridine yields the tetrahydrofuran derivative (XLII), which is reduced with LiBH4 to (5R-cis)-5-(2,4-difluoromethyl)-5-(iodomethyl)tetrahydrofuran-3-methanol (XLIII). Finally, this compound is condensed with sodium 1,2,4-triazole (XXXI) to afford (5R-cis)-5-(2,4-difluoromethyl)-5-(1,2,4-triazol-1-ylmethyl) tetrahydrofuran-3-methanol (XXXIII), already obtained in Scheme 22656201c.
| 【1】 Fromtling, R.A.; Castañer, J.; SCH-56592. Drugs Fut 1996, 21, 2, 160. |
| 【2】 Girijavallabhan, V.M.; Saksena, A.K.; Lovey, R.G.; Bennett, F.; Pike, R.E.; Wang, H.; Pinto, P.; Liu, Y.T.; Patel, N.; Ganguly, A.K.; SCH-56592, a novel orally active broad spectrum antifungal agent. 35th Intersci Conf Antimicrob Agents Chemother (Sept 17-20, San Francisco) 1995, Abst F61. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IXL) | 17092 | (4R)-4-heptyl-1,3-oxazolan-2-one | C10H19NO2 | 详情 | 详情 | |
| (XXXI) | 13104 | 1,2,4-Triazole, sodium derivative | 41253-21-8 | C2H2N3Na | 详情 | 详情 |
| (XXXIII) | 16343 | [(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methanol | C14H15F2N3O2 | 详情 | 详情 | |
| (XXXIV) | 13095 | m-Difluorobenzene; 1,3-Difluorobenzene | 372-18-9 | C6H4F2 | 详情 | 详情 |
| (XXXV) | 11291 | Dihydro-2,5-furandione; Succinic anhydride | 108-30-5 | C4H4O3 | 详情 | 详情 |
| (XXXVI) | 17089 | 4-(2,4-difluorophenyl)-4-oxobutyric acid | 110931-77-6 | C10H8F2O3 | 详情 | 详情 |
| (XXXVII) | 17090 | 4-(2,4-difluorophenyl)-4-pentenoic acid | C11H10F2O2 | 详情 | 详情 | |
| (XXXVIII) | 17091 | 4-(2,4-difluorophenyl)-4-pentenoyl chloride | C11H9ClF2O | 详情 | 详情 | |
| (XXXIX) | 17092 | (4R)-4-heptyl-1,3-oxazolan-2-one | C10H19NO2 | 详情 | 详情 | |
| (XL) | 17093 | (4R)-3-[4-(2,4-difluorophenyl)-4-pentenoyl]-4-heptyl-1,3-oxazolan-2-one | C21H27F2NO3 | 详情 | 详情 | |
| (XLI) | 17094 | (4R)-3-[(2S)-4-(2,4-difluorophenyl)-2-(hydroxymethyl)-4-pentenoyl]-4-heptyl-1,3-oxazolan-2-one | C22H29F2NO4 | 详情 | 详情 | |
| (XLII) | 17095 | (4R)-3-[[(3S,5R)-5-(2,4-difluorophenyl)-5-(iodomethyl)tetrahydro-3-furanyl]carbonyl]-4-heptyl-1,3-oxazolan-2-one | C22H28F2INO4 | 详情 | 详情 | |
| (XLIII) | 17096 | [(3R,5R)-5-(2,4-difluorophenyl)-5-(iodomethyl)tetrahydro-3-furanyl]methanol | C12H13F2IO2 | 详情 | 详情 |