Formic Acid → 7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one

Participants

Reaction Steps

To a suspension of 25.0 g of 2-chloro-5-fluoropyridin-3-amine, 3.8 g of bis(tricyclohexyl phosphine)palladium (II) chloride and 1.5 g of 2-(di-tert-butylphosphino)biphenyl in 75 mL of butyl acrylate, 44.1 g of diisopropylethylamine was added, 15.7 g of formic acid was added dropwise thereto at room temperature, and the mixture was refluxed for 3 hours. To the reaction mixture, 32.1 g of diisopropylethylamine and 11.5 g of formic acid were added at 100° C., and the mixture was refluxed for 5 hours. The reaction mixture was cooled to 80° C., 50 mL of toluene and 75 mL of water were added thereto and the resultant mixture was cooled to room temperature. The solid product was obtained by filtration, and washed using in the order of toluene and water to give 18.0 g of 7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one as a white solid.

Provenance & Evidence