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

HRID 3021

Reaction equation

HRID 3021 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].Cl[C:12]([F:18])([F:17])C(OC)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:17][CH:12]([F:18])[O:10][C:9]1[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[OH:1]

Participants

5

Reactant 3

HCID 87683,4-DihydroxybenzaldehydeHCID 11430Potassium CarbonateHCID 73935Methyl chlorodifluoroacetate

Product 1

HCID 27582954-(Difluoromethoxy)-3-hydroxybenzaldehydeYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3,4-Dihydroxybenzaldehyde (0.50 g, 3.62 mmol, Aldrich), methyl chlorodifluoroacetate (0.52 g, 3.62 mmol, Aldrich) and potassium carbonate (0.50 g, 3.62 mmol) were combined in DMF (5.0 mL) under an argon atmosphere. After stirring at 60°-65° C. for 3 h, DMF was removed in vacuo and the residue was partioned between aqueous 3N HCl and ether. The aqueous layer was extracted three times with ether. The combined organic extracts were washed with water, with brine, were dried (MgSO4), filtered and evaporated. The residue was purified by flash chromatography (silica gel, 25% ethyl acetate/hexanes) to provide the title compound as a white solid (0.20 g, 38%). mp 83°-85° C.

Workup

  1. customDMF was removed in vacuo
  2. extractionThe aqueous layer was extracted three times with ether
  3. washThe combined organic extracts were washed with water, with brine
  4. dry with materialwere dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography (silica gel, 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e57e5ba30ba5446d9ef33fda5e7bc0ab
Source dataset
uspto-grants-1998_03
Patent number
US05731477

Linked notes

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