Water → 4-(Difluoromethoxy)-3,5-dimethoxybenzaldehyde

HRID 468693Notes

Reaction equation

HRID 468693 reaction equation
Cl[C:2]([F:8])([F:7])C(OC)=O.O[C:10]1(OC)[CH:17]=[CH:16][C:13]([CH:14]=[O:15])=[CH:12][CH:11]1[O:18][CH3:19].[C:22](=O)([O-])[O-:23].[K+].[K+].[OH2:28]>CN(C=O)C>[F:7][CH:2]([F:8])[O:28][C:10]1[C:11]([O:18][CH3:19])=[CH:12][C:13]([CH:14]=[O:15])=[CH:16][C:17]=1[O:23][CH3:22]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 73935Methyl chlorodifluoroacetateHCID 866503554-Hydroxy-3,4-dimethoxybenzaldehyde

Product 1

HCID 7105984-(Difluoromethoxy)-3,5-dimethoxybenzaldehydeYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
67.5 °C

Procedure

Methyl chlorodifluoroacetate (0.58 mL, 5.5 mmol) was added to a suspension of 4-hydroxy-3,4-dimethoxybenzaldehyde (0.50 g, 2.7 mmol) and potassium carbonate (0.76 g, 5.5 mol) in DMF (5.0 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 crude product was recrystallised from EtOAc/petrol providing 4-(difluoromethoxy)-3,5-dimethoxybenzaldehyde (0.25 g, 39%) as a colourless crystalline solid; mp 113-115° C.; δH (400 MHz, CDCl3) 3.95 (s, 6H, OCH3), 6.65 (t, J=74 Hz, 1H, OCHF2), 7.15 (s, 2H, H2, H6), 9.91 (s, 1H, CHO); δC (100 MHz, CDCl3) δ6.5, 106.3, 116.2 (t, J=256 Hz), 134.1, 153.5, 190.8; νmax 831, 1048, 1099, 1330, 1600, 1699, 2854 cm−1.

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 crude product was recrystallised from EtOAc/petrol

Sources & evidence

ORD record
ord-82ff59ce80314f98b1f58463600fd8da
Source dataset
uspto-grants-2014_01
Patent number
US08624056B2

Reaction notes

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