Potassium Phosphate, Tribasic → HCID 136160552, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (Intermediate 31-4; 348 g, 1169 mmol) (80% strength by proton NMR), 6-chloro-3,5-dimethylpyrazine-2-carboxamide (217 g, 1169 mmol) and potassium phosphate tribasic (298 g, 1403 mmol) in DME (3.6 L), ethanol (0.9 L) and water (1.8 L) was stirred. The mixture was degassed with nitrogen for 30 minutes at 30° C. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (8.60 g, 10.5 mmol) was then added to the suspension. The reaction was further degassed for 10 minutes before being heated to 80° C., stirred for 4 hours. The reaction was cooled to 25° C. The solvents were then removed in vacuo until a slurry in water remained. A solution of citric acid (640 g) in water (6.0 L) was then added slowly with stirring. The suspension was filtered, washed with water (2×2.5 L), MTBE (2.5 L), sucked dry on the sinter and then dried at 65° C. in a vacuum over for 48 hours. Gave 6-(3-fluoro-4-hydroxyphenyl)-3,5-dimethylpyrazine-2-carboxamide (295 g, 97%) as a light brown solid.

Provenance & Evidence