反应详情

温度

100 °C

1.03 g (2.64 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 30 mL of dimethylformamide under argon atmosphere, 11.5 mL (79.2 mmol) of ethyl 4-bromobutyrate, 1.83 g (13.3 mmol) of potassium carbonate and 3.96 g (26.4 mmol) of sodium iodide were added and the mixture was stirred at 100° C. for 48 hours. The reaction solution was cooled on ice, an aqueous saturated solution of ammonium chloride was added and the mixture was extracted with ethyl acetate. The organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform:acetonitrile=25:l) and recrystallized from ethyl acetate/n-hexane to give 720 mg of 5-(3-ethoxycarbonylpropylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one (yield: 54%).

1. temperatureThe reaction solution was cooled on ice
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride
4. dry with materialdried over anhydrous sodium sulfate
5. distillationThe solvent was distilled off under reduced pressure
6. customthe residue was purified by silica gel column chromatography (chloroform:acetonitrile=25:l)
7. customrecrystallized from ethyl acetate/n-hexane