Carbon Dioxide → HCID 86685086, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-bromo-2-fluoro-1-methylbenzene (21.9 g, 116 mmol) in THF (100 mL) was added lithium diisopropylamide (LDA) (2 M solution in THF, 69 mL, 139 mmol) at −78° C. After being stirred at −78° C. for 1 h, the reaction was treated with excess solid carbon dioxide, and stirred while the reaction temperature slowly rose to room temperature. The mixture was concentrated and then partitioned between 4N NaOH and ethyl acetate. The aqueous phase was adjusted to pH 2 with 2N HCl and then extracted three times with ethyl acetate. The combined extracts were washed with water and brine, dried over with anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluted with EA to give methyl 6-bromo-2-fluoro-3-methylbenzoic acid (23.3 g, 86.2%) as a white solid.

Provenance & Evidence