2,6-DIFLUORO-4-METHOXYBENZOIC ACID

124-38-9

93343-10-3

123843-65-2

A hexane solution (31.2 mL) of 1.6 M n-butyllithium was slowly added dropwise to a tetrahydrofuran (120 mL) solution of 1,3-difluoro-5-methoxybenzene (5.54 g) at -78 °C under nitrogen protection. The reaction temperature of -78 °C was maintained and stirring was continued for 30 min. Subsequently, sublimated dry ice (8.46 g) was added to the reaction system through a silica gel tube and the reaction was continued at -78 °C. The reaction mixture was gradually warmed to room temperature and stirred for 5 min. After completion of the reaction, the reaction solution was acidified by slowly adding 1 N hydrochloric acid solution to the reaction solution at 0 °C. The reaction mixture was extracted with mixed ethyl acetate/tetrahydrofuran solvent and the organic phases were combined. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure and the resulting solid was washed with hexane and diisopropyl ether to give 2,6-difluoro-4-methoxybenzoic acid (5.00 g) as a white solid. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 3.83 (3H, s), 6.82 (2H, d, J = 11.0 Hz), 13.43 (1H, brs).