Carbon Dioxide → 3-Bromo-2-fluoro-5-methylbenzoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (1.8 mL, 12.7 mmol) in THF (20 mL) at −10° C., n-BuLi (0.68 g, 10.6 mmol) was added and the reaction was stirred for 1 hour at −10° C. and was then cooled to −78° C. A solution of 2-bromo-1-fluoro-4-methylbenzene (2.0 g, 10.6 mmol) in THF (10 mL) was added in dropwise and the reaction was stirred for 1 hour after which excess solid carbon dioxide (4.76 g, 106 mmol) was added. After 30 minutes the reaction mixture was allowed to warm to room temperature, allowing for pressure release, and was quenched with water. The resulting layers were separated and the aqueous portion was extracted with Et2O. The aqueous layer was then acidified with aqueous 6.0 M HCl solution and the resulting white precipitate was extracted into Et2O. The combined organic portions were dried (MgSO4), and concentrated in vacuo to afford 3-bromo-2-fluoro-5-methylbenzoic acid (2.1 g, 9.0 mmol, 85%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 2.37 (s, 3H) 7.60 (dd, J=5.9, 1.8 Hz, 1H) 7.75 (dd, J=6.2, 1.8 Hz, 1H).

Provenance & Evidence