反応式
[F:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])=[CH:4][C:3]=1[OH:14].N1C=CN=C1.[CH3:20][C:21]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])[CH3:22]>CN(C=O)C>[Si:24]([O:14][C:3]1[CH:4]=[C:5]([CH:12]=[CH:13][C:2]=1[F:1])[C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])([C:21]([CH3:23])([CH3:22])[CH3:20])([CH3:26])[CH3:25]参加物
実験手順
To a solution of 4-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide (1.90 g, 9.55 mmol) in DMF (8 mL) was added imidazole (740 mg, 10.8 mmol) and TBDMSCl (1.62 g, 10.8 mmol) at room temperature. The reaction mixture was stirred for 48 h and quenched with saturated NaHCO3. The solution was extracted with ether (3×) and the combined ether portions washed with LiCl (10%), dried over Na2SO4, filtered and concentrated. The resulted colorless oil was purified by ISCO chromatography (120 g column) using hexanes/EtOAc (0-100% over 30 min) to give 3-(tert-butyldimethylsilyloxy)-4-fluoro-N-methoxy-N-methylbenzamide (RT=10-12 minutes) as a colorless oil (2.00 g, 67% yield). LCMS: RT=2.06 min [M+H] 314.22 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz (CDCl3) 7.26 ppm, 2H, m; 7.02 ppm, 1H, m; 3.50 ppm, 3H, s; 3.31 ppm, 3H, s; 0.97 ppm, 9H, s, 0.16 ppm, 6H, s.
後処理
- customquenched with saturated NaHCO3
- extractionThe solution was extracted with ether (3×)
- washthe combined ether portions washed with LiCl (10%)
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe resulted colorless oil was purified by ISCO chromatography (120 g column)
- customhexanes/EtOAc (0-100% over 30 min)
出典と根拠
- ORDレコード
- ord-0aed554ac622414e8474aaa643383c1b
- 出典データセット
- uspto-grants-2010_09
- 特許番号
- US07790770B2
関連ノート
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