Potassium Hydroxide → N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

Participants

Reaction Conditions

Reaction Steps

With ice-bath cooling, 1.05 g (2.95 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 7 g of toluene and admixed with stirring with 820 mg (3.69 mmol) of chlorodiphenylphosphine. The mixture was heated at 108° C. for 3 h. After cooling to room temperature, 553 mg (4.43 mmol) of aqueous potassium hydroxide solution (45 percent strength) and 97.5 mg (0.29 mmol) of tetrabutylammonium bromide was added, and the mixture was stirred vigorously at 60° C. for 1 h. The heat source was removed and the reaction mixture, which was still warm, was admixed with 20 ml of water. The mixture was slowly cooled to 4° C., and the precipitated solid was filtered off. The product was washed with cold water and toluene and dried under reduced pressure at 40° C. 1.04 g (64.1 percent; content: 97.6 percent) of N-[5-(diphenylphosphinoylmethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide was isolated in the form of a colorless solid.

Provenance & Evidence