The general procedure for the synthesis of 2-(3,5-bis-trifluoromethyl-phenyl)-2-methylpropanoic acid using nerapitant impurity 20 as a starting material was as follows: lithium hydroxide monohydrate (2.13 g, 50.6 mmol) was added to α,α-dimethyl-3,5-bis(trifluoromethyl)benzeneacetic acid methyl ester (5.3 g, 16.88 mmol) in a methanol (60 mL), water (20 mL) and tetrahydrofuran (20 mL) in a suspension. The mixture was degassed and the reaction was stirred at room temperature for 3 days. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was suspended in 1 M hydrochloric acid and extracted with ethyl acetate. The organic phases were combined and dried over anhydrous magnesium sulfate, followed by evaporation of the solvent under reduced pressure to afford the target product 2-(3,5-bis-trifluoromethyl-phenyl)-2-methylpropanoic acid as a colorless solid (5.05 g, 100% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.84 (2H, s), 7.80 (1H, s), 1.68 (6H, s).
