2,2,2-Trifluoroethanol → 5-[(2,2,2-trifluoroethoxy)methyl]-2-furoic acid

HRID 341566Notes

Reaction equation

HRID 341566 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].C[O:10][C:11]([C:13]1[O:14][C:15]([CH2:18]Cl)=[CH:16][CH:17]=1)=[O:12]>CN(C=O)C.CCOC(C)=O>[F:3][C:4]([F:8])([F:7])[CH2:5][O:6][CH2:18][C:15]1[O:14][C:13]([C:11]([OH:12])=[O:10])=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydride3×HCID 75065Methyl 5-(chloromethyl)-2-furoate

Product 1

HCID 9404105-[(2,2,2-trifluoroethoxy)methyl]-2-furoic acidYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 60 mg, 1.50 mmol) was added to 2,2,2-trifluoroethanol (99 μL, 1.38 mmol) in anhydrous DMF (1 mL) and the mixture was stirred under nitrogen for 20 min. 5-Chloromethylfuran-2-carboxylic acid methyl ester (200 mg, 1.15 mmol) was then added and the mixture was stirred at room temperature for 18 h, then at 60 C for 3 h, then at 100 C for 3 h. Sodium hydride (60% dispersion in mineral oil, 30 mg, 0.75 mmol) was added under nitrogen and the reaction mixture was stirred at room temperature for 18 h. Sodium hydride (60% dispersion in mineral oil, 30 mg, 0.75 mmol) was added and the mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc (30 mL) then washed with saturated aq. sodium bicarbonate (4×6 mL), saturated aq. ammonium chloride (2×6 mL) and then brine (6 mL). The aqueous extractions were combined and brought to pH 1 by the addition of 2M HCl and then extracted with DCM (5 mL). The combined organic extractions were washed with water (3×6 mL), then brine (6 mL) and then dried over sodium sulfate and evaporated under vacuum to afford the title compound (123 mg, 48%), which was used without further purification. Method C HPLC-MS: (MH+) requires m/z=225. Found: m/z=252, Rt=1.15 min (97%).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 h
  2. waitat 60 C for 3 h
  3. waitat 100 C for 3 h
  4. stirringthe reaction mixture was stirred at room temperature for 18 h
  5. stirringthe mixture was stirred at room temperature for 3 h
  6. washthen washed with saturated aq. sodium bicarbonate (4×6 mL), saturated aq. ammonium chloride (2×6 mL)
  7. extractionThe aqueous extractions
  8. additionbrought to pH 1 by the addition of 2M HCl
  9. extractionextracted with DCM (5 mL)
  10. extractionThe combined organic extractions
  11. washwere washed with water (3×6 mL)
  12. dry with materialbrine (6 mL) and then dried over sodium sulfate
  13. customevaporated under vacuum

Sources & evidence

ORD record
ord-a96e5caeaf1147b0b57f099de2ce2354
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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