Trifluoroacetic acid → 3-Chloro-4-(4-chloro-3-(trifluoromethyl)phenoxy)-2-fluorobenzoic acid

HRID 2359326Notes

Reaction equation

HRID 2359326 reaction equation
[Cl:1][C:2]1[C:3]([F:16])=[C:4]([CH:12]=[CH:13][C:14]=1F)[C:5]([O:7]C(C)(C)C)=[O:6].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=1[C:25]([F:28])([F:27])[F:26].C(=O)([O-])[O-].[K+].[K+].FC(F)(F)C(O)=O>O.CS(C)=O>[Cl:1][C:2]1[C:3]([F:16])=[C:4]([CH:12]=[CH:13][C:14]=1[O:24][C:21]1[CH:22]=[CH:23][C:18]([Cl:17])=[C:19]([C:25]([F:28])([F:26])[F:27])[CH:20]=1)[C:5]([OH:7])=[O:6]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 805204-Chloro-3-(trifluoromethyl)phenolHCID 58046346Tert-butyl 3-chloro-2,4-difluorobenzoate

Product 1

HCID 580463433-Chloro-4-(4-chloro-3-(trifluoromethyl)phenoxy)-2-fluorobenzoic acidYield 37.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

tert-Butyl 3-chloro-2,4-difluorobenzoate (Preparation 154, 0.249 g, 1.00 mmol), 4-chloro-3-(trifluoromethyl)phenol (0.196 g, 1.00 mmol) and potassium carbonate (210 mg, 1.5 mmol) were added to dimethyl sulfoxide (6 mL) and stirred at ambient temperature for 4 hours, then another 18 hours at 70° C. The reaction mixture was diluted with water and extracted three times with ethyl ether. The combined organic phase was dried over anhydrous magnesium sulfate and the solvent removed in vacuo to leave a residue. The residue was purified by silica gel column chromatography eluting with 0-10% ethyl acetate in hexanes. The desired fractions were combined and the solvent removed in vacuo. The residue was dissolved in trifluoroacetic acid (0.50 mL, 6.5 mmol) and stirred for 18 hours. The solvent was removed in vacuo and the residue triturated with dichloromethane. The resulting precipitate was collected by filtration and vacuum dried to afford the title compound as a white solid (140 mg).

Workup

  1. customanother 18 hours
  2. customat 70° C
  3. extractionextracted three times with ethyl ether
  4. dry with materialThe combined organic phase was dried over anhydrous magnesium sulfate
  5. customthe solvent removed in vacuo
  6. customto leave a residue
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with 0-10% ethyl acetate in hexanes
  9. customthe solvent removed in vacuo
  10. stirringstirred for 18 hours
  11. customThe solvent was removed in vacuo
  12. customthe residue triturated with dichloromethane
  13. filtrationThe resulting precipitate was collected by filtration and vacuum
  14. customdried

Sources & evidence

ORD record
ord-4981fd0ee4e14c5d80c81f90ccab5135
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

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