Potassium Carbonate → 3-Methyl-4-[2-(trifluoromethyl)phenyl]benzoic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 4-bromo-3-methylbenzoate (20 g, 87 mmol), 2-(trifluoromethyl)benzeneboronic acid (24.9 g, 131 mmol), potassium carbonate (24 g, 175 mmol) and bis(tricyclohexylphosphine)palladium (II) dichloride (65 mg, 0.1 mmol) was prepared in dioxane (200 mL) and water (50 mL) under N2 atmosphere. The mixture was heated at 100° C. for 3 hours. A 5N aqueous solution of NaOH (100 mL) was added and the reaction mixture was stirred at 100° C. for one additional hour. The reaction mixture was cooled at RT and the aqueous layer was removed. The organic layer was filtered through a celite pad, concentrated until 75 mL under reduced pressure, diluted with water (125 mL) and washed with MTBE (2×200 mL). The aqueous layer was acidified to pH 1 with a 5N aqueous solution of HCl (25 mL) and extracted with MTBE (2×100 mL). The organic layers were combined, dried (Na2SO4) and filtered through a celite pad. The solution was concentrated until 100 mL, then heptane was added (200 mL). The mixture was concentrated until 100 mL. The precipitate was filtered off and rinsed twice with heptane, then dried under reduced pressure to give the title compound as a white powder (22.5 g, 92%). HPLC (Method A), Rt 4.4 min (purity: 100%). LC/MS (Method B): 279.0 (M−H)−. 1H NMR (DMSO-d6, 300 MHz) δ 13.0 (s, 1H), 7.87 (m, 2H), 7.80 (dd, J=7.9, 1.6 Hz, 1H), 7.75 (m, 1H), 7.64 (m, 1H), 7.34 (d, J=7.6 Hz, 1H), 7.23 (d, J=7.9 Hz, 1H), 2.02 (s, 3H).

Provenance & Evidence