Dimethylformamide → 3-(Difluoromethoxy)-2,4,5-trifluorobenzoic acid

HRID 1440091Notes

Reaction equation

HRID 1440091 reaction equation
CN(C)C=O.[F:6][C:7]1[C:15]([OH:16])=[C:14]([F:17])[C:13]([F:18])=[CH:12][C:8]=1[C:9]([OH:11])=[O:10].[OH-].[Na+].Cl[CH:22]([F:24])[F:23]>O>[F:23][CH:22]([F:24])[O:16][C:15]1[C:7]([F:6])=[C:8]([CH:12]=[C:13]([F:18])[C:14]=1[F:17])[C:9]([OH:11])=[O:10]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 6372ChlorodifluoromethaneHCID 14798Sodium HydroxideHCID 27342702,4,5-Trifluoro-3-hydroxybenzoic Acid

Product 1

HCID 150237813-(Difluoromethoxy)-2,4,5-trifluorobenzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

20 ml of dimethylformamide, followed by 4.97 g (0.026 mole) of 2.4,5-trifluoro-3-hydroxybenzoic acid [(XXIII), X=X'=F], were added in portions, whilst ice-cooling, to a solution of 2.18 g (0.052 mole) of sodium hydroxide in 5 ml of water. Thereafter the solution was stirred for 30 minutes, whilst ice-cooling. The reaction mixture was then transferred to a 200 ml stainless steel autoclave, and 100 ml of dimethylformamide containing 24.0 g (0.277 mole) of chlorodifluoromethane were added to it. The mixture was then stirred at between 100° and 110° C. for 5 hours under pressure. At the end of this time, the reaction mixture was poured into water and extracted with chloroform. The chloroform extracts were washed with water and dried over anhydrous sodium sulfate; the solvent was then removed by evaporation under reduced pressure. The residue was purified by column chromatography through silica gel using a 9:1 by volume mixture of ethyl acetate and ethanol as the eluent, to afford 2.00 g of 3-difluoromethoxy-2,4,5-trifluorobenzoic acid as a colorless powder.

Workup

  1. additionwere added in portions, whilst ice-
  2. temperaturecooling
  3. additionwere added to it
  4. stirringThe mixture was then stirred at between 100° and 110° C. for 5 hours under pressure
  5. extractionextracted with chloroform
  6. washThe chloroform extracts were washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe solvent was then removed by evaporation under reduced pressure
  9. customThe residue was purified by column chromatography through silica gel using a 9:1
  10. additionby volume mixture of ethyl acetate and ethanol as the eluent

Sources & evidence

ORD record
ord-bf313f4ac6874aa4a010de7612d7406c
Source dataset
uspto-grants-1996_03
Patent number
US05496951

Reaction notes

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