反应详情

To a mixture of (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one ((S)-II; prepared as described in U.S. Pat. No. 5,808,095) (60.0 g, 0.167 mol) and K2CO3 (27.7 g, 0.20 mol) in THF (600 mL) was added formaldehyde (37% solution in H2O, 240 mL, 3.2 mol) followed by H2O (300 mL). The lightly turbid mixture was stirred at room temperature for 3 hours, and diluted with diethyl ether (1000 mL). The organic layer was separated. The aqueous layer was washed with ether (200 mL×2). The combined organic layer was washed with brine, dried over Na2SO4. Evaporation of solvents provided the title compound as a white dry foam (64.5 g, 99% yield). LC/MS m/e: 390 (MH+), 96% purity. 1H NMR (CDCl3): δ 7.79 (dd, J=1.0, 3.0 Hz, 1H) 7.34 (m, 3H), 7.24 (m, 1H), 6.75 (dd, J=1.5, 6.5 Hz, 1H), 5.45 (m, 1H), 5.28 (m, 1H), 3.50 (s, 3H).

1. customprepared
2. customThe organic layer was separated
3. washThe aqueous layer was washed with ether (200 mL×2)
4. washThe combined organic layer was washed with brine
5. dry with materialdried over Na2SO4
6. customEvaporation of solvents