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

Participants

Reaction Conditions

Reaction Steps

2.03 g (5.69 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 13 g of toluene and, with ice-bath cooling, admixed with 1.67 g (7.51 mmol) of chlorodiphenylphosphine in 2 g of toluene. The mixture was heated at 111° C. for 2.5 h. After cooling to room temperature, 1.08 g (8.66 mmol) of a 45 percent strength potassium hydroxide solution and 175 mg (0.574 mmol) of tetrabutylammonium chloride was added, and the mixture was stirred vigorously at 60° C. for 2 h. 30 ml of water was added to the warm reaction mixture. The mixture was briefly stirred at 60° C. and slowly cooled to 4° C., and the precipitated solid was filtered off. The product was washed with cold water (10 ml) and cold toluene (10 ml) and dried under reduced pressure at 40° C. 2.66 g (84.1 percent; content: 96.6 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