Sodium Carbonate → Methyl 5-bromo-2'-fluoro-4'-methylbiphenyl-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

Methyl 3-bromo-5-iodo-benzoate (13 g) and 2-fluoro-4-methylphenylboronic acid (6 g) were dissolved in DMF (120 mL) at room temperature. The solution was then cooled down to 0° C. with ice bath. To this solution was added aq. sodium carbonate (6 g in 50 mL of water), Pd(dppf)Cl2 (3 g) and DMF (10 mL). After the addition, the reaction was warmed up slowly to room temperature. The reaction mixture was then stirred at room temperature for 4 hrs. Solvent was evaporated under reduced pressure. The residue was re-dissolved in EtOAc (200 mL) washed with HCl (1M) 3×200 mL), sat. NaHCO3 (3×100 mL), brine (3×100 mL) and water (3×100 mL). The organic layer was separated and concentrated. The crude product was then purified with column chromatography (silica gel, eluted with EtOAc/Hexane, 0 to 1%) to give pure compound. Note a second column can be done to further remove unwanted bis cross coupled by-product.

Provenance & Evidence