Carbon Dioxide → 4-Bromo-2,6-difluorobenzoic acid

Participants

Reaction Conditions

Reaction Steps

n-BuLi (220 mL, 550 mmol, 2.5 M) was added dropwise to a solution of diisopropylamine (61 g) in THF (500 mL) with stirring at −50° C. under N2. After the addition, the reaction mixture was stirred at −50° C. for 15 minutes, and then warmed to 0° C. for 1 hour. The reaction was cooled to −50° C. and then a solution of 3,5-difluorobromobenzene (96 g, 0.5 mole) in THF (500 mL) was added dropwise. After the addition, the reaction mixture was stirred at −50° C. for 2 hours and then dry ice (about 200 g) was added portion-wise. The resulting mixture was warmed gradually to room temperature and stirred overnight. The mixture was concentrated under reduced pressure, and the resulting residue was partitioned between CH2Cl2 (1 L) and water (1 L). An aqueous NaOH solution was added to adjust the pH of the mixture to 10. The organic layer was discarded and the water phase was adjust the pH to 2 with HCl solution. The mixture was extracted with CH2Cl2 (3×400 mL), and the extracts were combined, dried over MgSO4, filtered and evaporated under vacuum to provide the title compound (45 g) as a white solid.

Provenance & Evidence