反应详情

温度

60 °C

A mixture of 4′-fluoro-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.31 g, 1.00 mmol), 2-(chloromethyl)-3-(trifluoromethyl)pyridine hydrochloride (0.29 g, 1.50 mmol) and cesium carbonate (0.98 g, 3.00 mmol) in N,N′ dimethylformamide (10 mL) was heated at 60° C. for 2 h and was filtered while hot. The filtrate was allowed to cool to ambient temperature and water was added, causing a precipitate to be deposited. The solid was collected by filtration, washed with water (50 mL) and dried under vacuum. The residue was recrystallized from N,N′ dimethylformamide/water to afford 4′-fluoro-1′-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.39 g, 82%) as a beige solid: mp 245-247° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.68 (d, J=4.5 Hz, 1H), 8.27 (d, J=7.65 Hz, 1H), 7.59 (dd, J=7.8, 4.9 Hz, 1H), 7.30 (ddd, J=8.2, 8.2, 5.8 Hz, 1H), 6.86 (d, J=9.0 Hz, 1H), 6.82 (d, J=7.8 Hz, 1H), 6.54 (s, 1H), 6.49 (s, 1H), 5.25 (ABq, J=17.4 Hz, 2H), 4.79 (q, J=9.4 Hz, 2H), 4.22-4.10 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 176.5, 157.9 (d, 1JC-F=247 Hz), 154.6, 152.3, 152.1 (d, 5JC-F=1.2 Hz), 144.9 (d, 4JC-F=8.9 Hz), 144.3, 137.6, 135.1 (q, 4JC-F=4.9 Hz), 130.8 (d, 4JC-F=8.6 Hz), 125.6 (q, 1JC-F=274 Hz), 123.0, 122.9 (d, 2JC-F=32.3 Hz), 119.4, 117.1 (d, 3JC-F=19.3 Hz), 111.5, 109.9 (d, 3JC-F=19.9 Hz), 105.7 (d, 5JC-F=2.9 Hz), 98.4, 77.4, 64.1, 63.5, 56.0 (d, 5JC-F=1.7 Hz), 42.3 (q, 5JC-F=3.3 Hz); MS (ES+) m/z 460.9 (M+1).

1. filtrationwas filtered while hot
2. temperatureto cool to ambient temperature
3. additionwater was added
4. filtrationThe solid was collected by filtration
5. washwashed with water (50 mL)
6. customdried under vacuum
7. customThe residue was recrystallized from N,N′ dimethylformamide/water