反应详情

温度

70 °C

A solution of 3,5-difluoroaniline (5 g, 38.8 mmol), methyl-3-methoxyacrylate (4.6 ml, 42.7 mmol) and sodium methoxide solution (25% in MeOH, 12 ml) in toluene (50 ml) under Argon was stirred at 70° C. for 3 h. More sodium methoxide solution (25% in MeOH, 6 mL) added and reaction stirred overnight. Still more sodium methoxide solution (25% in MeOH, 12 mL) and methyl-3-methoxyacrylate (5 mL, 46.4 mmol) were then added and reaction was heated at 70° C. for 5 h. MeOH was added and volume of toluene was reduced to about 10 ml. The residue was acidified to pH 7 using a saturated solution of ammonium chloride, solid ammonium chloride and 5N HCl. The aqueous phase was extracted using ethyl acetate (2×500 ml). The combined organic phases were dried, evaporated and the residue was chromatographed on silica gel, eluting with 0-100% ethyl acetate-40-60° C. petroleum ether to afford the impure desired compound (12 g, 126%).

1. customreaction
2. customreaction
3. extractionThe aqueous phase was extracted
4. customThe combined organic phases were dried
5. customevaporated
6. customthe residue was chromatographed on silica gel
7. washeluting with 0-100% ethyl acetate-40-60° C. petroleum ether