Water → 4-Cyclohexyl-3-(trifluoromethyl)benzoic acid

HRID 423345Notes

Reaction equation

HRID 423345 reaction equation
[CH:1]1([C:7]2[CH:15]=[CH:14][C:10]([C:11](N)=[O:12])=[CH:9][C:8]=2[C:16]([F:19])([F:18])[F:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-:20].[K+].O>C(O)C>[CH:1]1([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:20])=[O:12])=[CH:9][C:8]=2[C:16]([F:19])([F:18])[F:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 962Water2×HCID 14797Potassium Hydroxide2×HCID 592017944-Cyclohexyl-3-(trifluoromethyl)benzamide

Product 1

HCID 574300334-Cyclohexyl-3-(trifluoromethyl)benzoic acidYield 89.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-cyclohexyl-3-(trifluoromethyl)benzamide (D67) (822 mg, 3.03 mmol) in ethanol (40 ml) was added potassium hydroxide (1.700 g, 30.3 mmol) and water (5 ml) and the reaction heated to 90° C. block temperature for 3 h and stirred at room temperature for 16 h. Further potassium hydroxide (1.700 g, 30.3 mmol) was added and the reaction heated at reflux for 27 h. A further 5 mL of water was added and the reaction heated for 66 hours (weekend). The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate (25 mL) and aqueous hydrochloric acid (2M, 25 mL). The aqueous layer was further extracted with ethyl acetate (25 mL) and the combined organic phases dried (MgSO4), filtered and the solvent removed in vacuo to give the title compound as a white solid (737 mg). δH (methanol-d4, 400 MHz): 8.24 (1H, d), 8.18 (1H, dd), 7.68 (1H, d), 2.98 (1H, t), 1.72-1.95 (5H, m), 1.30-1.58 (5H, m). MS (ES): C14H15F3O2 requires 272; found 271 (M−H+).

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux for 27 h
  3. temperaturethe reaction heated for 66 hours (weekend)
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue partitioned between ethyl acetate (25 mL) and aqueous hydrochloric acid (2M, 25 mL)
  6. extractionThe aqueous layer was further extracted with ethyl acetate (25 mL)
  7. dry with materialthe combined organic phases dried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-c396caba1fec417d9acf5cee9c160a0f
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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