Hydrochloric Acid → 2-Hydroxy-3-(trifluoromethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

A solution of Example 42A (14.1 g, 68.4 mmol) in THF (68 mL) was cooled to −20° C. and n-butyllithium (30.1 mL of a 2.5 M solution in hexanes, 75.0 mmol) was added slowly, keeping the temperature at 0° C. After 70 min at −5 to 5° C., the reaction mixture was cooled to −20° C. and CO2 gas was bubbled through the brown slurry, keeping the temperature ≦−10° C. The reaction went from a brown slurry to a dark purple solution to a yellow solution. After 10 min, the reaction mixture was cooled further to −20° C. and treated with 2N HCl (68 mL, 140 mmol). To facilitate the reaction mixture, additional concentrated HCl (17 mL, total 5 equiv of 4M HCl) was added. After 30 min, MTBE (70 mL) was added, and the organic portion was extracted with 2N NaOH (70 mL) and water (70 mL). The aqueous layer was acidified with 2N HCl (98 mL) and extracted with dichloromethane (2×140 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to give the title compound (14.8 g, 71.8 mmol, 99%) as a yellow solid which was used without further purification. MS (DCI/NH3) m/z 207 (M+H)+.

Provenance & Evidence