Carbon Dioxide → 4-Fluoro-2-methylbenzoic acid

Participants

Reaction Conditions

Reaction Steps

To a cooled (−78° C.) solution of 2-bromo-5-fluorotoluene (10.0 g, 52.9 mmol) in diethyl ether (100 mL) was added dropwise n-butyllithium (1.6 M in hexane, 21.2 mL, 52.9 mmol). The mixture was stirred for 5 min, and slowly warmed to 0° C. Dry ice (100 g, 2.27 mol) was slowly added to the mixture while stirring, and it was allowed to warm to rt over 16 h. The mixture was adjusted to pH=2, and extracted with ethyl acetate (3×20 mL). The organic phase was concentrated and the resulting yellow residue suspended in water (100 mL). The suspension was adjusted to pH=12 with 2 N NaOH, and washed with diethyl ether. The aqueous phase was then acidified to pH=2 with 2 N HCl, and extracted with diethyl ether (3×50 mL). The organic extract was washed with water, dried (MgSO4), and concentrated under reduced pressure to afford the product (5.0 mg, 61%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 2.53 (s, 3H), 7.06-7.17 (m, 2H), 7.87 (dd, 1H), 12.85 (s, 1H).

Provenance & Evidence