Hydrogen Peroxide → (s)-2-((1-Methylpyrrolidin-2-yl)methoxy)-5-(trifluoromethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of Example 57B (12.0 g, 42 mmol) in ethanol (50 mL) was added 15 mL of water and then warmed to 40° C. Then sodium hydroxide (7.8 mL, 148 mmol) was added followed by hydrogen peroxide (7.3 mL, 127 mmol) in four portions, each one hour apart. The reaction mixture was heated at 40° C. for 4 additional hours. Sodium hydroxide (6.7 mL, 127 mmol) was added followed by 10 mL of water. After stirring at 80° C. for 12 hours, the reaction mixture was cooled, concentrated under reduced pressure, diluted with 100 mL of water, and extracted with diethyl ether (2×25 mL). The aqueous solution was neutralized to pH 7 with 6N aqueous HCl and concentrated under reduced pressure to dryness. The residue was suspended in dichloromethane (100 mL), the solution heated to 60° C. and filtered; this process was repeated 3 times. The combined filtrates were concentrated under reduced pressure and azeotroped with toluene to afford 10.2 g (80%) of the title compound. MS (ESI+) m/z 304 (M+H)+.

Provenance & Evidence