Vanillin → 4-(Difluoromethoxy)-3-methoxybenzaldehyde

HRID 468687Notes

Reaction equation

HRID 468687 reaction equation
Cl[C:2]([F:8])([F:7])C(OC)=O.[O:9]=[CH:10][C:11]1[CH:19]=[CH:18][C:16]([OH:17])=[C:13]([O:14][CH3:15])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[F:7][CH:2]([F:8])[O:17][C:16]1[CH:18]=[CH:19][C:11]([CH:10]=[O:9])=[CH:12][C:13]=1[O:14][CH3:15]

Participants

6

Reactant 3

HCID 1183VanillinHCID 11430Potassium CarbonateHCID 73935Methyl chlorodifluoroacetate

Product 1

HCID 31612494-(Difluoromethoxy)-3-methoxybenzaldehydeYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
67.5 °C

Procedure

Methyl chlorodifluoroacetate (1.4 mL, 13 mmol) was added to a suspension of vanillin (1.0 g, 6.6 mmol) and potassium carbonate (2.0 g, 14 mol) in DMF (10 mL). The suspension was heated to 65-70° C. for 16 h and the suspension was diluted with water. The aqueous phase was extracted with EtOAc and the combined organic fractions were washed with saturated aqueous NaHCO3, water, brine, dried and concentrated. The residue was purified by column chromatography, eluting with 10% EtOAc/petrol to give 4-(difluoromethoxy)-3-methoxybenzaldehyde (0.54 g, 41%) as a colourless oil; δH (400 MHz, CDCl3) 3.95 (s, 3H, OCH3), 6.60 (t, J=74 Hz, 1H, OCHF2), 7.30 (d, J5,6=8.0 Hz, 1H, H5), 7.45 (dd, J5,6=8.0, J2,6=2.0 Hz, 1H, H6), 7.50 (d, J2,6=2.0 Hz, 1H, H2), 9.93 (s, 1H, CHO); δC (100 MHz, CDCl3) 56.2, 110.9, 115.5 (t, J=256 Hz), 121.5, 125.0, 134.5, 144.9, 151.5, 190.8.

Workup

  1. extractionThe aqueous phase was extracted with EtOAc
  2. washthe combined organic fractions were washed with saturated aqueous NaHCO3, water, brine
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography
  6. washeluting with 10% EtOAc/petrol

Sources & evidence

ORD record
ord-5abfc0e55060424d91d4c4115a7f979f
Source dataset
uspto-grants-2014_01
Patent number
US08624056B2

Reaction notes

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