Potassium Carbonate → 1-(Difluoromethoxy)-2-fluoro-3-nitrobenzene

HRID 1527449Notes

Reaction equation

HRID 1527449 reaction equation
Cl[C:2]([F:7])([F:6])C([O-])=O.[Na+].C(=O)([O-])[O-].[K+].[K+].[F:15][C:16]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][CH:19]=[CH:18][C:17]=1[OH:25]>CN(C=O)C.O>[F:6][CH:2]([F:7])[O:25][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([N+:22]([O-:24])=[O:23])[C:16]=1[F:15]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734985Sodium chlorodifluoroacetateHCID 233406732-Fluoro-3-nitrophenol

Product 1

HCID 463115911-(Difluoromethoxy)-2-fluoro-3-nitrobenzene

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
110 °C

Procedure

To a mixture of sodium 2-chloro-2,2-difluoroacetate (7.14 g, 46.8 mmol) and potassium carbonate (3.50 g, 25.3 mmol) in DMF (10 mL) and water (2.5 mL) at 110° C. was added a solution of 2-fluoro-3-nitrophenol (2 g, 12.65 mmol) in DMF (10 mL) and the mixture was stirred at 110° C. for 6 h. After cooling down, the mixture was quenched with water and extracted with EtOAc. The organic layer was then washed with water, brine and dried over Na2SO4, filtered and concentrated. The crude material was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 1:1). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.79 (td, 1H), 7.45 (t, 1H), 5.15 (m, 1H), 7.44 (m, 1H). tR (HPLC conditions f): 2.09 min.

Workup

  1. temperatureAfter cooling down
  2. customthe mixture was quenched with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was then washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 1:1)
  9. custom2.09 min.

Sources & evidence

ORD record
ord-54b9cbf42ddf4860ba5da26d4e5da058
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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