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

Participants

Reaction Conditions

Reaction Steps

To a solution of Example 24A (12.0 g, 42 mmol) in ethanol (50 mL) was added 15 mL of water and then warmed to 40° C. Then 50% sodium hydroxide (7.8 mL, 148 mmol) was added to the above reaction mixture followed by 50% hydrogen peroxide (7.3 mL, 127 mmol), which was added in 4 portions, each portion one hour apart. The reaction mixture was heated 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 (6.7 mL, 127 mmol) was added followed by 10 mL of water. After stirring at 80° C. for 12 h, the reaction mixture was concentrated under reduced pressure to remove ethanol and diluted with 100 mL of water. The resulting solution was washed (2×25 mL) with diethyl ether. The aqueous solution was neutralized to pH 7 with 6N 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