Hydrochloric Acid → 2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxylic acid

HRID 1282443Notes

Reaction equation

HRID 1282443 reaction equation
Br[C:2]1[C:7]2[CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH2:18][F:19])([CH2:16][F:17])[CH:3]=1.[C:20]([O-:23])(=[O:22])C.[K+].[I-].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C(=O)C>[F:17][CH2:16][C:4]1([CH2:18][F:19])[CH:3]=[C:2]([C:20]([OH:23])=[O:22])[C:7]2[CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=[CH:11][C:6]=2[O:5]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 184244094-bromo-2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran

Product 1

HCID 98796402,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-bromo-2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran (1.72 g), potassium acetate (2.00 g), potassium iodide (0.85 g), triphenylphosphine (27 mg), palladium acetate (11 mg) and N,N-dimethylacetamide (10 ml) was stirred under a CO atmosphere at 120° C. for 9 hours. To the reaction mixture, 2 N HCl was added and the precipitating crystals were recovered by filtration. To the recovered crystals, ethyl acetate was added and the insoluble matter was filtered off; the filtrate was washed with a saturated aqueous solution of sodium thiosulfate and a saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate and concentrated under reduced pressure; the resulting residue was dissolved in a saturated aqueous solution of sodium hydrogencarbonate washed with dichloromethane; concentrated HCl was added to the resulting aqueous layer to make it acidic and the precipitating crystals were recovered by filtration. The recovered crystals were dissolved in ethyl acetate, dried with anhydrous magnesium sulfate and concentrated under reduced pressure; the resulting residue was recrystallized with a solvent consisting of a mixture of ethyl acetate and hexane, thereby giving 2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxylic acid (1.25 g) represented by the formula (C2-1) and having a melting point of 162-163° C.

Workup

  1. filtrationthe precipitating crystals were recovered by filtration
  2. additionTo the recovered crystals, ethyl acetate was added
  3. filtrationthe insoluble matter was filtered off
  4. washthe filtrate was washed with a saturated aqueous solution of sodium thiosulfate
  5. dry with materiala saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionthe resulting residue was dissolved in a saturated aqueous solution of sodium hydrogencarbonate
  8. washwashed with dichloromethane
  9. additionconcentrated HCl was added to the resulting aqueous layer
  10. filtrationthe precipitating crystals were recovered by filtration
  11. dissolutionThe recovered crystals were dissolved in ethyl acetate
  12. dry with materialdried with anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customthe resulting residue was recrystallized with a solvent
  15. additionconsisting of a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-e93ba94f5a9b4d6aa6b233e2f5446077
Source dataset
uspto-grants-2002_09
Patent number
US06455708B1

Reaction notes

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