反应详情

温度

0 °C

To 5-(4-fluoro-3-methoxyphenyl)-2-trifluoromethyl[1,8]naphthyridine (prepared as described in Example 34; 1.00 g, 3.1 mmol) in dichloromethane (20 mL) was added boron(III) bromide (9.31 mL of a 1 M solution in dichloromethane, 9.3 mmol) dropwise with stirring at 0° C., and the resulting mixture was stirred at 0° C. for 1 h. Methanol (2 mL) was added dropwise at 0° C. with stirring—Care! Large exotherm observed!—then the mixture was poured into saturated sodium hydrogencarbonate solution (50 mL). Effervescence was observed, and a yellow solid was precipitated, which was separated by filtration, washed with water and dried in a drying pistol at 60° C. This was 2-fluoro-5-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)phenol (881 mg, 92%). δH (400 MHz, DMSO) 7.01-7.04 (1H, m), 7.16 (1H, dd, J 2.3 and 8.2), 7.40 (1H, dd, J 8.2 and 11.3), 7.74 (1H, d, J 4.3), 8.09 (1H, d, J 8.6), 8.66 (1H, d, J 8.6), 9.27 (1H, d, J 4.3), 10.30 (1H, s). m/z (ES+) 309 [MH]+.

1. stirringthe resulting mixture was stirred at 0° C. for 1 h
2. customa yellow solid was precipitated
3. customwhich was separated by filtration
4. washwashed with water
5. customdried in a drying pistol at 60° C