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

HRID 717263

Reaction equation

HRID 717263 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][C@H:4]([O:7][C:8]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:9]=2[C:10]#N)[CH2:3]1.[OH-:20].[Na+].[OH:22]O>C(O)C.O>[CH3:1][N:2]1[CH2:6][CH2:5][C@H:4]([O:7][C:8]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:9]=2[C:10]([OH:22])=[O:20])[CH2:3]1

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium Hydroxide2×HCID 66698243(S)-2-(1-methylpyrrolidin-3-yloxy)-5-(trifluoromethyl)benzonitrile

Product 1

HCID 66698222(s)-2-(1-Methylpyrrolidin-3-yloxy)-5-(trifluoromethyl)benzoic acidYield 80%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
40 °C

Procedure

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)+.

Workup

  1. additionwas added in 4 portions
  2. customeach portion one hour
  3. additionwas added
  4. stirringThen the reaction mixture was stirred at 80° C.
  5. temperaturecooled
  6. concentrationconcentrated
  7. dissolutiondissolved in 100 mL of water
  8. washThe resultant solution was washed with diethyl ether (2×25 mL)
  9. concentrationand then concentrated to dryness
  10. temperatureheated to 60° C.
  11. filtrationfiltered
  12. concentrationThe combined filtrates were concentrated
  13. customazeotroped with toluene

Sources & evidence

ORD record
ord-54d7133895a9499d8b9b5632c30a295d
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Linked notes

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