3,4-Dihydroxybenzaldehyde → 4-(Difluoromethoxy)-3-hydroxybenzaldehyde

HRID 2427860Notes

Reaction equation

HRID 2427860 reaction equation
[OH-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[OH:12])[CH:7]=[O:8].Cl[C:14]([F:19])([F:18])C([O-])=O.[Na+]>CN(C)C=O.O>[F:18][CH:14]([F:19])[O:12][C:11]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][C:4]=1[OH:3]

Participants

6

Reactant 3

HCID 87683,4-DihydroxybenzaldehydeHCID 14798Sodium HydroxideHCID 2734985Sodium chlorodifluoroacetate

Product 1

HCID 27582954-(Difluoromethoxy)-3-hydroxybenzaldehydeYield 44.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Sodium hydroxide (4.8 g, 120 mmoles) is added to a solution of 3,4-dihydroxybenzaldehyde (16.6 g, 120 mmol) and sodium chlorodifluoroacetate (18.3 g, 120 mmol) in dimethylformamide (150 mL) and water (3 mL). The mixture is heated to 120° C. and stirred at this temperature for 2 hours. The solvent is removed by vacuum distillation and aqueous hydrochloric acid (20 mL) is added to the residue. The mixture is extracted with diethyl ether (2×50 ml), the combined organic layers are washed with water and brine and the solvent removed under reduced pressure. The crude product is purified by chromatography on silica gel (hexane/ethyl acetate 8:2) to furnish 4-difluoromethoxy-3-hydroxybenzaldehyde as a colourless solid (10 g).

Workup

  1. customThe solvent is removed by vacuum distillation and aqueous hydrochloric acid (20 mL)
  2. additionis added to the residue
  3. extractionThe mixture is extracted with diethyl ether (2×50 ml)
  4. washthe combined organic layers are washed with water and brine
  5. customthe solvent removed under reduced pressure
  6. customThe crude product is purified by chromatography on silica gel (hexane/ethyl acetate 8:2)

Sources & evidence

ORD record
ord-6eb932ca148f40c8afdbece9b862f237
Source dataset
uspto-grants-2011_06
Patent number
US07968724B2

Reaction notes

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