Toluene → 4-Isopropoxy-3-(trifluoromethyl)benzoic acid

Participants

Reaction Steps

Methyl 3-bromo-4-iso-propyloxybenzoate (828 mg; 3.03 mmol) in DMF (25 ml) was treated with potassium trifluoroacetate (922 mg; 6.06 mmol), copper (I) iodide (1.15 g; 6.06 mmol) and toluene (50 ml). The resulting mixture was heated at reflux for 1.5 h (Dean and Stark with removal of ca 50 ml of distillate) followed by reflux for 18 h then cooled. The mixture was poured into Et2O (100 ml) and H2O (100 ml). The two-phase mixture was stirred at room temperature for 0.5 h then filtered through Celite. The two phases were separated, the aq. phase further extracted with EtO (50 ml) and the organic extracts combined, washed with saturated, aq. Na2S2O3, H2O, saturated brine, dried (MgSO4) and evaporated in vacuo to give a brown oil. This was dissolved in MeOH (ca 20 ml) and treated with 2M NaOH (2 ml; 4 mmol) and the resulting solution heated at reflux for 3 h. The volatiles were removed in vacuo and the residue partitioned between EtOAc and H2O. The phases were separated, the aq. phase acidified to pH1 with 2M HCl in the presence of EtOAc and the phases separated. The aq. phase was further extracted with EtOAc, the extracts combined, washed with H2O, saturated brine, dried (MgSO4) and evaporated to dryness in vacuo to give the title compound as a white solid (671 mg; 89%).

Provenance & Evidence