反应详情

温度

65 °C

Cesium carbonate (352 g, 1.08 mol) was added to a mechanically stirred solution of methyl 6-(4-hydroxyphenyl)-1-naphthoate (199 g, 0.72 mol) in dimethylformamide (1 L) under N2. The resulting suspension was heated to 65° C. for 30 min followed by addition of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole (280 g, 0.92 mol) in dimethylformamide (500 mL). The mixture was heated at 65° C. for 18 h, cooled to room temperature and partitioned between ethyl acetate (1 L) and water (1 L). The ethyl acetate layer was backwashed with water (2×1 L) and concentrated to a thick black syrup. This syrup was triturated with hexane (500 mL) and ethyl acetate (300 mL) for 2 h. Filtration gave 190 g of the product as beige crystals. 1H NMR (DMSO-d6); δ 8.77 (d, J=9 Hz, 1H), 8.23-8.20 (m, 2H), 8.09 (d, J=7 Hz, 1H), 7.92 (dd, J=2, 9 Hz, 1H), 7.69 (d, J=9 Hz, 2H), 7.63-7.51 (m, 4H), 6.91 (d, J=9 Hz, 2H), 4.86 (s, 2H), 3.92 (s, 3H), 3.45 (septet, J=7 Hz, 1H), 1.33 (d, J=7 Hz, 6H). ESI-LCMS m/z 546 (M+H)+.

1. temperatureThe mixture was heated at 65° C. for 18 h
2. temperaturecooled to room temperature
3. custompartitioned between ethyl acetate (1 L) and water (1 L)
4. concentrationconcentrated to a thick black syrup
5. customThis syrup was triturated with hexane (500 mL) and ethyl acetate (300 mL) for 2 h
6. filtrationFiltration