Potassium Phosphate, Tribasic → HCID 136160557, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-chloro-3,5-dimethylpyrazine-2-carboxamide (Intermediate A) (20.17 g, 108.67 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (26.3 g, 119.53 mmol) and tripotassium phosphate (34.6 g, 163.00 mmol) in DME (500 mL), MeOH (250 mL) and water (125 mL) was degassed before addition of (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (DCM adduct) (4.47 g, 5.43 mmol). The reaction mixture was heated to 80° C., under nitrogen, and left to stir for 1 hour. The reaction mixture was allowed to cool to room temperature and then evaporated. The residue was partitioned between water (1 L), 2M HCl aq. (1 L) and EtOAc (1 L). The aqueous was re-extracted with EtOAc (2 L) and the combined organics washed with brine (1 L), dried (MgSO4) and evaporated to give crude product. The aqueous was filtered and the solid was washed with water (2 L) to give pure product. The crude product from the organic layer was purified by flash silica chromatography, elution gradient 20 to 80% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 6-(4-hydroxyphenyl)-3,5-dimethylpyrazine-2-carboxamide (22.00 g, 83%) as a cream solid.

Provenance & Evidence