Pyridine, hydrofluoride (1:1) → 4-Fluoro-2-trifluoromethoxyphenol

HRID 1911495Notes

Reaction equation

HRID 1911495 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([O:13][C:14]([F:17])([F:16])[F:15])[CH:7]=1.[FH:18].N1C=CC=CC=1.O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C>[F:18][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([O:13][C:14]([F:17])([F:16])[F:15])[CH:7]=1

Participants

6

Reactant 4

HCID 64774Pyridine, hydrofluoride (1:1)HCID 113330044-Amino-2-(trifluoromethoxy)phenolHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 23668193Sodium Nitrite

Product 1

HCID 867621784-Fluoro-2-trifluoromethoxyphenolYield 17.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

33 mg (0.48 mmol) of sodium nitrite was added to a solution of 77 mg (0.4 mmol) of 4-amino-2-trifluoromethoxyphenol in 0.8 mL of 65% (w/w) hydrofluoric acid/pyridine under argon atmosphere with stirring at an outer bath temperature of 0˜5° C. The outer bath was heated to 5˜10° C. and the mixture was stirred for 30 min until the solution turned brownish red. To the above solution were successively added 90 mg (0.4 mmol) of stannous chloride dihydrate and 105 mg (0.4 mmol) of tetrabutylammonium fluoride trihydrate. The solution was slowly heated to—100° C., allowed to react at this temperature for 3.0 h until it was dark brown. The reaction was stopped, naturally cooled, poured into ice water, and 15 mL of ethyl acetate was added. The organic layer was isolated, and the water layer was extracted with 15 mL×2 of ethyl acetate. The organic layers were combined, successively washed with 30 mL of water and 30 mL of saturated saline, dried over anh. MgSO4, filtered and concentrated. The residue was purified by preparative silica gel thin layer chromatography (mobile phase: petroleum ether: ethyl acetate=2:1) to obtain 14 mg of a pale yellow oil. Yield 17.9%.

Workup

  1. temperatureThe outer bath was heated to 5˜10° C.
  2. stirringthe mixture was stirred for 30 min until the solution
  3. customto react at this temperature for 3.0 h until it
  4. temperaturenaturally cooled
  5. additionwas added
  6. customThe organic layer was isolated
  7. extractionthe water layer was extracted with 15 mL×2 of ethyl acetate
  8. washsuccessively washed with 30 mL of water and 30 mL of saturated saline
  9. dry with materialdried over anh. MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by preparative silica gel thin layer chromatography (mobile phase: petroleum ether: ethyl acetate=2:1)

Sources & evidence

ORD record
ord-2a20566a94b04d5582e5433a9844a441
Source dataset
uspto-grants-2013_12
Patent number
US08604065B2

Reaction notes

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