Dimethylformamide → 4-(difluoromethoxy)-3,5-dimethylbenzaldehyde

HRID 1485069Notes

Reaction equation

HRID 1485069 reaction equation
[OH:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[CH3:11].CN(C)C=O.Cl[C:18]([F:23])([F:22])C([O-])=O.[Na+].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O>[F:22][CH:18]([F:23])[O:1][C:2]1[C:3]([CH3:11])=[CH:4][C:5]([CH:6]=[O:7])=[CH:8][C:9]=1[CH3:10]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 752223,5-Dimethyl-4-hydroxybenzaldehydeHCID 2734985Sodium chlorodifluoroacetate

Product 1

HCID 21202814-(difluoromethoxy)-3,5-dimethylbenzaldehydeYield 94.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 4-hydroxy-3,5-dimethylbenzaldehyde (2.00 g), N,N-dimethylformamide (54.0 mL) and water (6.00 mL), sodium chlorodifluoroacetate (6.09 g) and potassium carbonate (3.68 g) were added and the mixture was stirred at 120° C. for 4.5 hours. After cooling the reaction mixture to room temperature, water was added to it and two extractions were conducted with ethyl acetate. The combined organic layers were washed with water four times and thereafter washed with saturated brine. After drying over anhydrous magnesium sulfate, the desiccant was removed by filtration and the filtrate was then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=97:3-88:12) to give the titled compound as a colorless solid (2.53 g).

Workup

  1. additionwere added
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. washThe combined organic layers were washed with water four times
  4. washwashed with saturated brine
  5. dry with materialAfter drying over anhydrous magnesium sulfate
  6. customthe desiccant was removed by filtration
  7. concentrationthe filtrate was then concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=97:3-88:12)

Sources & evidence

ORD record
ord-668bfcda6a354697b6778098f28d5cf7
Source dataset
uspto-grants-2016_08
Patent number
US09422240B2

Reaction notes

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