反应详情

A mixture of 12 (Scheme 3) (500 mg, 1.47 mmol), trifluoroacetaldehyde ethyl hemiacetal (0.35 mL, 2.94 mmol) and 4-toluenesulfonic acid monohydrate (280 mg, 1.47 mmol) in ethanol (25 mL) was heated to reflux for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92) to afford title compound 318 (470 mg, 1.01 mmol, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.42 (d, J=5.5 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.72 (d, J=0.8 Hz, 1H), 7.67 (s, 1H), 7.29 (t, J=9.2 Hz, 1H), 7.08-7.02 (m, 2H), 3.86 (dd, J=9.2, 2.0 Hz, 1H), 6.52 (d, J=5.5 Hz, 1H), 5.68 (qd, J=10.4, 5.2 Hz, 1H), 3.72 (s, 3H), 3.76-3.59 (m, 2H), 1.15 (t, J=7.0 Hz, 3H). LRMS (M+1) 467.0 (100%).

1. temperaturewas heated
2. temperatureto reflux for 48 h
3. concentrationThe reaction mixture was concentrated
4. customthe residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 5:95 to 8:92)