反应详情

温度

55 °C

A mixture of 4-methoxycarbonyl-5-methyl(tetrahydropyran-2-yl)-3-(2-chloro-6-fluoro-phenyl)isoxazole (2.95 g, 7.98 mmol), 2N NaOH (8.0 ml, 16.0 mmol), MeOH (20 ml), and THF (10 ml) was heated to 55° C. for 4 h. After cooling to 0° C., HCl (1N) was added until pH 3. The mixture was extracted with ethyl acetate (3×), and the combined extracts were washed (brine), dried (MgSO4), filtered, and concentrated to give the crude acid. The crude acid was dissolved in dichloromethane (50 ml) along with 2-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide (3.80 g, 12.0 mmol), EDCI (3.33 g, 17.4 mmol), HOAt (2.72 g, 20.00 mmol), and DMAP (0.10 g, 0.80 mmol) and stirred at room temperature overnight. The mixture was applied to a silica gel column and eluted with dichloromethane/acetone (gradient) to give the title compound (2.61 g, 41%).

1. temperatureAfter cooling to 0° C.
2. extractionThe mixture was extracted with ethyl acetate (3×)
3. washthe combined extracts were washed (brine)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customto give the crude acid
8. washeluted with dichloromethane/acetone (gradient)