Potassium Phosphate, Tribasic → Methyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetate

関与物質

反応条件

反応手順

To a degassed solution of 3,5-dimethyl-6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carboxamide (Intermediate 7-6; 196 mg, 0.55 mmol) in DME (6 mL), ethanol (1.5 mL) and water (1.5 mL) was added tripotassium phosphate (141 mg, 0.67 mmol), methyl 2-(3-chloro-4-(trifluoromethylsulfonyloxy)phenyl)acetate (Intermediate 1-2; 185 mg, 0.55 mmol) followed by (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (DCM adduct) (36.5 mg, 0.04 mmol). The resulting mixture was stirred at 80° C. under nitrogen for 4 hours. The reaction mixture was allowed to cool to ambient temperature, evaporated and partitioned between EtOAc (75 mL) and saturated brine (50 mL) then filtered through celite. The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20 to 80% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetate (110 mg, 48.4%) as a white solid.

情報源と証拠