Water → 5-(4-chlorobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Participants

Reaction Steps

1.01 g (2.59 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 20 ml of dimethylformamide under argon atmosphere, 228 mg of sodium hydride (60% oil dispersion) and 1.5 ml of 1-bromo-4-chlorobutane were added under ice-cooling and the mixture was stirred at room temperature for 3 hours. 228 mg of sodium hydride (60% oil dispersion) and 1.5 ml of 1-bromo-4-chlorobutane were further added and the mixture was stirred for additional 1 hour. Water was added to the reaction solution and the mixture was extracted three times with ethyl acetate. The organic layer was washed twice with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1) to give 396 mg (32%) of 5-(4-chlorobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one.

Provenance & Evidence