Water → 2-Bromo-4-chloro-1-(difluoromethoxy)benzene

HRID 1466586Notes

Reaction equation

HRID 1466586 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].Cl[C:11]([F:16])([F:15])C([O-])=O.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[O:9][CH:11]([F:16])[F:15]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 696702-Bromo-4-chlorophenolHCID 2734985Sodium chlorodifluoroacetate

Product 1

HCID 463115372-Bromo-4-chloro-1-(difluoromethoxy)benzeneYield 48.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-bromo-4-chlorophenol (4.98 g, 24.0 mmol) in 25 mL DMF was added sodium chlorodifluoroacetate (8.42 g, 55.2 mmol), cesium carbonate (10.97 g, 33.67 mmol) and 2.5 mL water. The reaction was stirred at 100° C. for 16 hours. The reaction mixture was partitioned between ethyl acetate and water, and the organic portion washed with brine, dried over magnesium sulfate, and concentrated. The crude product was purified by flash chromatography on silica gel (0 to 20% ethyl acetate in heptanes) to yield 2.98 g (48%) of 2-bromo-4-chloro-1-(difluoromethoxy)benzene as a clear, colorless oil. LCMS (ESI) no m/z signal; 1H NMR (400 MHz, DMSO-d6) δ: 7.90 (d, 1H), 7.54 (dd, 1H), 7.38 (d, 1H), 7.28 (t, 1H).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washthe organic portion washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography on silica gel (0 to 20% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-df599684ba66488ebcb2d84c403ab2f7
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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