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

Temperature

40 °C

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)+.

1. additionwas added in 4 portions
2. customeach portion one hour
3. temperatureThe reaction mixture was heated at 40° C. for 4 more hours
4. additionwas added
5. concentrationthe reaction mixture was concentrated under reduced pressure
6. customto remove ethanol
7. additiondiluted with 100 mL of water
8. washThe resulting solution was washed (2×25 mL) with diethyl ether
9. concentrationconcentrated under reduced pressure to dryness
10. temperaturethe solution heated to 60° C.
11. filtrationfiltered
12. concentrationThe combined filtrates were concentrated under reduced pressure
13. customazeotroped with toluene

ORD record

ord-baa9c99ead4a4e3aa272b027d213ddbc

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895592B2