Sodium Carbonate → Methyl 5'-amino-2',4'-difluoro-2-methylbiphenyl-4-carboxylate

Participants

Reaction Steps

5-bromo-2,4-difluoroaniline (500 mg, 2.40 mmol), methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (INTERMEDIATE 16, 797 mg, 2.88 mmol), sodium carbonate (2.40 mL, aq., 2M, 2.88 mmol), 1,1′-bis(diphenylphosphino) ferrocene-palladium dichloride dichloromethane adduct (196 mg, 0.24 mmol) and ethanol (15 ml) were heated in an 80° C. oil bath for 3 hours then allowed to cool to ambient overnight. Volatiles were removed under reduced pressure. The pot residue was worked up w/DCM/brine/Na2SO4/filtration/concentration to afford a dark oil. The resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge). The column was eluted by a 0% to 40% EtOAc/hexanes gradient mixture. Related fractions were pooled and concentrated in vacuo to afford the title compound. LCMS (ESI) calc.=277.09; found=278.03 (M+1)+.

Provenance & Evidence