Hydrogen Peroxide → (s)-2-(1-Methylpyrrolidin-3-yloxy)-5-(trifluoromethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of Example 97A (10.9 g, 40.5 mmol) in ethanol (50 mL) and water (15 mL) at 40° C. was added sodium hydroxide (7.5 mL, 142 mmol, 50% aqueous solution), followed by hydrogen peroxide (7.0 mL, 122 mmol, 50% aqueous solution), which was added in 4 portions, each portion one hour apart. The reaction was stirred at 40° C. for 4 more hours. The reaction was monitored by LC/MS. After almost all the nitrile was converted to the amide, sodium hydroxide (6.4 mL, 122 mmol, 50% aqueous solution) was added followed by 10 mL of water. Then the reaction mixture was stirred at 80° C., cooled, concentrated and dissolved in 100 mL of water. The resultant solution was washed with diethyl ether (2×25 mL). The aqueous solution was neutralized to pH 7 with 6N HCl. and then concentrated to dryness. The precipitate was suspended in ethanol/dichloromethane (100 mL, 1:1), heated to 60° C. and filtered. This process was repeated 3 times. The combined filtrates were concentrated and azeotroped with toluene to obtain 8.5 g (80%) of the title compound. MS (ESI+) m/z 290 (M+H)+.

Provenance & Evidence