Water → 2-(Difluoromethoxy)-4-fluoro-1-nitrobenzene

HRID 576065Notes

Reaction equation

HRID 576065 reaction equation
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:9]=[CH:10][C:11]([N+:15]([O-:17])=[O:16])=[C:12]([OH:14])[CH:13]=1.COC(=O)[C:21](Cl)([F:23])[F:22].O>CN(C)C=O>[F:22][CH:21]([F:23])[O:14][C:12]1[CH:13]=[C:8]([F:7])[CH:9]=[CH:10][C:11]=1[N+:15]([O-:17])=[O:16]

Participants

6

Reactant 4

HCID 962WaterHCID 99375-Fluoro-2-nitrophenolHCID 11430Potassium CarbonateHCID 73935Methyl chlorodifluoroacetate

Product 1

HCID 463115882-(Difluoromethoxy)-4-fluoro-1-nitrobenzeneYield 71.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (2.42 g, 17.5 mmol) was added to a solution of 5-fluoro-2-nitrophenol (785 mg, 5.00 mmol) in N,N-dimethylformamide (10 mL), and the mixture was stirred at room temperature for 20 min. Chlorodifluoroacetic acid methyl ester (1.33 mL, 12.5 mmol) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 30 min and then stirred at an external temperature of 90° C. for 3 hr. After cooling, water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over anhydrous magnesium sulfate and then the desiccant was filtered off, followed by concentration under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→4:1) to afford 2-(difluoromethoxy)-4-fluoro-1-nitrobenzene as a pale yellow oil (745 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. stirringstirred at an external temperature of 90° C. for 3 hr
  3. temperatureAfter cooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationthe desiccant was filtered off
  8. concentrationfollowed by concentration under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→4:1)

Sources & evidence

ORD record
ord-48b518a5ce6d439b97ab2c8b6ce45b97
Source dataset
uspto-grants-2015_05
Patent number
US09035059B2

Reaction notes

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