Ethyl Acetate → 6-(4-Bromo-2-fluorophenoxy)-2-fluoro-3-methoxybenzoic acid

Participants

Reaction Steps

To a 1 L RB was added 4-bromo-2-fluorophenol (18.85 mL, 169 mmol), 6-bromo-2-fluoro-3-methoxybenzoic acid (40 g, 161 mmol), copper (I) trifluoromethanesulfonate toluene complex (4.16 g, 8.03 mmol), ethyl acetate (1.6 mL, 16.06 mmol) and cesium carbonate (105 g, 321 mmol) in dry toluene (300 mL). The reaction mixture was stirred at rt for 15 min and heated at 110° C. for overnight. The toluene was decanted and the resulting green sticky precipitate was washed with excess hexanes and then acidified by addition of 6N aqueous HCl. The resulting solution was added water and extracted with EtOAc 3×. The light brown organic phase was then washed by brine and dried by MgSO4. The solution was filtered and concentrated in vacuo to give the crude material 6-(4-bromo-2-fluorophenoxy)-2-fluoro-3-methoxybenzoic acid (45.4 g, 126 mmol, 79% yield) as a brown solid. It was used for next step without further purification.

Provenance & Evidence