Methane → 2-(2,2,2-Trifluoroethoxy)benzoic acid

HRID 460424Notes

Reaction equation

HRID 460424 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].CC(C)([O-])C.[Na+].Cl[C:14]1[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([OH:18])=[O:17].Cl.C>C(OCC)(=O)C.O.CN(C=O)C>[F:1][C:2]([F:6])([F:5])[CH2:3][O:4][C:14]1[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([OH:18])=[O:17]

Participants

9

Reactant 5

HCID 297MethaneHCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 83742-Chlorobenzoic AcidHCID 23676156Sodium t-butoxide

Product 1

HCID 115286442-(2,2,2-Trifluoroethoxy)benzoic acidYield 88%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2,2,2-trifluoroethanol (40.0 g) and DMF (100 ml) was added sodium tert-butoxide (23.0 g) at 0° C. The solution was stirred at 20 to 25° C. for 1 hour at which point 2-chlorobenzoic acid (25.0 g) was added followed by cupric bromide (2.0 g). The mixture was stirred at 120° C. for 5 hours, cooled to 10° C., and water (30 ml) was added followed by 20% HCl solution (90 ml). The solution was extracted with dichloromethane (3×50 ml). The combined organic layers were washed with water (3×50 ml) and the volume was concentrated to 90 ml. Hexane (150 ml) was added to the residues, and the mixture was concentrated to volume of 120 ml and a further portion of hexane (30 ml) was added. The mixture was heated at 50° C. for 30 minutes and then stirred at room temperature for 1 hour. The solids were filtered to yield the crude product. This material was dissolved in ethyl acetate (50 ml), charcoal (1.7 g) was added and the mixture was stirred at room temperature a further 2 hours. The solution was filtered through Celite™ and crystallized from ethyl acetate/hexane to yield the pure product (30.9 g, yield 88.0%) as a white solid, m.p. 85–86° C.

Workup

  1. additionwas added
  2. temperaturecooled to 10° C.
  3. extractionThe solution was extracted with dichloromethane (3×50 ml)
  4. washThe combined organic layers were washed with water (3×50 ml)
  5. concentrationthe volume was concentrated to 90 ml
  6. additionHexane (150 ml) was added to the residues
  7. concentrationthe mixture was concentrated to volume of 120 ml
  8. additiona further portion of hexane (30 ml) was added
  9. temperatureThe mixture was heated at 50° C. for 30 minutes
  10. stirringstirred at room temperature for 1 hour
  11. filtrationThe solids were filtered
  12. customto yield the crude product
  13. stirringthe mixture was stirred at room temperature a further 2 hours
  14. filtrationThe solution was filtered through Celite™
  15. customcrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-e1aa6ddc7f9b4c77ab17112539292a64
Source dataset
uspto-grants-2007_03
Patent number
US07196197B2

Reaction notes

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