反应详情

温度

0 °C

To a solution of 3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (4.00 g, 11.2 mmol) in anhydrous dichloromethane (80.0 mL) was added diisopropylethylamine (6.10 mL) and thionyl chloride (2.77 g, 23.5 mmol) under nitrogen at 0° C. The reaction mixture was stirred at 0° C. for 1 h and concentrated in vacuo to dryness. The residue was dissolved in THF/acetic acid (7:3, 100 mL) followed by the addition of Zn dust (3.08 g, 47.1 mmol) in one portion. The reaction mixture was stirred at ambient temperature for 16 h, filtered and the residue was washed with ethyl acetate (30.0 mL). The filtrate was concentrated in vacuo to dryness. The residue was dissolved in ethyl acetate (200 mL), washed with saturated ammonium chloride (3×50.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography to give the title compound (2.92 g, 76%): 1H NMR (300 MHz, CDCl3) δ 8.64 (br, 1H), 8.26 (d, 1H), 7.52 (d, 1H), 7.05 (dd, 1H), 6.53 (s, 1H), 6.25 (s, 1H), 5.84 (d, 2H), 5.02 (s, 1H), 3.86-3.75 (m, 2H), 1.76-1.67 (m, 2H), 1.33-1.28 (m, 4H), 0.85 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 178.5, 157.4, 150.9, 147.8, 147.5, 141.6, 133.2, 121.7, 118.7, 114.1, 106.4, 101.2, 101.1, 46.5, 39.8, 28.9, 27.3, 22.3, 13.9; MS (ES+) m/z 341 (M+1).

1. concentrationconcentrated in vacuo to dryness
2. dissolutionThe residue was dissolved in THF/acetic acid (7:3, 100 mL)
3. stirringThe reaction mixture was stirred at ambient temperature for 16 h
4. filtrationfiltered
5. washthe residue was washed with ethyl acetate (30.0 mL)
6. concentrationThe filtrate was concentrated in vacuo to dryness
7. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
8. washwashed with saturated ammonium chloride (3×50.0 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationThe filtrate was concentrated in vacuo to dryness