反应详情

To a solution of 5-fluoro-3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-1-{[5-(trifluoromethyl)-2-furyl]methyl}-1,3-dihydro-2H-indol-2-one (3.34 g, 7.18 mmol) in anhydrous tetrahydrofuran (80.0 mL) was added tributylphosphine (2.18 g, 2.70 mL, 10.8 mmol) under nitrogen. A solution of di-tert-butyl azodicarboxylate (2.49 g, 10.8 mmol) in anhydrous tetrahydrofuran (25.0 mL) was added over 10 min. The reaction solution was stirred for 1 h, and quenched with saturated ammonium chloride (30.0 mL). After the solvent was removed under reduced pressure, the gummy material was extracted with ethyl acetate (3×75.0 mL). The organic layer was washed with 10% aqueous HCl solution (2×25.0 mL), saturated aqueous sodium hydrogen carbonate (3×25.0 mL), brine (3×25.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography eluting with ethyl acetate/hexane (30%) to afforded the title compound (1.10 g, 34%) as a colorless solid: mp 139-141° C.; 1H NMR (300 MHz, CDCl3) δ 7.02-6.96 (m, 1H), 6.93-6.89 (m, 2H), 6.74-6.73 (m, 1H), 6.50 (s, 1H), 6.38 (d, 1H), 6.09 (s, 1H), 5.87 (dd, 2H), 4.95 (ABq, 2H), 4.78 (Abq, 2H); 13C NMR (75 MHz, CDCl3) δ 176.9, 161.5, 158.3, 155.9, 151.7, 149.2, 142.6, 137.1, 137.1, 133.7, 118.6, 115.6, 115.3, 112.7, 112.4, 112.0, 109.7, 109.6, 109.4, 102.8, 101.7, 93.8, 80.1, 58.6, 37.1; MS (ES+) m/z 448.2 (M+1).

1. customquenched with saturated ammonium chloride (30.0 mL)
2. customAfter the solvent was removed under reduced pressure
3. extractionthe gummy material was extracted with ethyl acetate (3×75.0 mL)
4. washThe organic layer was washed with 10% aqueous HCl solution (2×25.0 mL), saturated aqueous sodium hydrogen carbonate (3×25.0 mL), brine (3×25.0 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo to dryness
8. washeluting with ethyl acetate/hexane (30%)