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【结 构 式】 
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【分子编号】60548 【品名】[4-(3-nitrophenoxy)-2,3-dihydro-1H-inden-2-yl]methanol 【CA登记号】 |
【 分 子 式 】C16H15NO4 【 分 子 量 】285.29944 【元素组成】C 67.36% H 5.3% N 4.91% O 22.43% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reduction of 4-hydroxyindane-2-carboxylic acid ethyl ester (I) by means of LiAlH4 in THF gives the hydroxymethyl derivative (II), which is condensed with 3-fluoronitrobenzene (III) by means of K2CO3 in DMF to yield the diaryl ether (IV). The reduction of the nitro group of (IV) by means of H2 over Pd/C in THF/methanol affords the aniline derivative (V), which is treated with NaNO2 and H2SO4 and heated at 100 C to provide the phenol (VI). The condensation of (VI) with 4,4,4-trifluorobutylsulfonyl chloride (VII) by means of t-BuOK in THF leads to the racemic sulfonate (VIII), which is finally submitted to optical resolution by preparative chiral HPLC over Chiracel OD to furnish the target (R)-enantiomer.
| 【1】 Raddatz, S.; De Vry, J.-M.-V.; Mohrs, K.-H.; Dressel, J.; Matzke, M.; Mittendorf, J.; Mauler, F.; Schuhmacher, J.; Friedl, A.; Horvath, E.; Jork, R.; Keldenich, J.; Franz, J.; Spreyer, P.; Vöhringer, V.; Rock, M.-H. (Bayer AG); Aryl sulfonamides and analogues thereof and their use in the treatment of neurodegenerative diseases. DE 19740785; EP 0966436; JP 2001515470; US 2002072529; US 6262112; US 6573278; WO 9837061 . |
| 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) | 60546 | ethyl 4-hydroxy-2-indanecarboxylate | C12H14O3 | 详情 | 详情 | |
| (II) | 60547 | 2-(hydroxymethyl)-4-indanol | C10H12O2 | 详情 | 详情 | |
| (III) | 55147 | di(tert-butyl) (2R,4S,5R)-5-{(1R)-1-(acetylamino)-2-[(triisopropylsilyl)oxy]ethyl}-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C30H56N2O6Si | 详情 | 详情 | |
| (IV) | 60548 | [4-(3-nitrophenoxy)-2,3-dihydro-1H-inden-2-yl]methanol | C16H15NO4 | 详情 | 详情 | |
| (V) | 60549 | [4-(3-aminophenoxy)-2,3-dihydro-1H-inden-2-yl]methanol | C16H17NO2 | 详情 | 详情 | |
| (VI) | 60550 | 3-{[2-(hydroxymethyl)-2,3-dihydro-1H-inden-4-yl]oxy}phenol | C16H16O3 | 详情 | 详情 | |
| (VII) | 26779 | 1-butanesulfonyl chloride | 2386-60-9 | C4H9ClO2S | 详情 | 详情 |
| (VIII) | 60551 | 3-{[2-(hydroxymethyl)-2,3-dihydro-1H-inden-4-yl]oxy}phenyl 4,4,4-trifluoro-1-butanesulfonate | C20H21F3O5S | 详情 | 详情 |