Hydrochloric Acid → 4-(Difluoromethoxy)-3-hydroxybenzaldehyde

HRID 1765118Notes

Reaction equation

HRID 1765118 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].[Na+].Cl[C:13]([F:18])([F:17])C([O-])=O.[OH-].[Na+].Cl>CN(C=O)C>[F:17][CH:13]([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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 87683,4-DihydroxybenzaldehydeHCID 14798Sodium HydroxideHCID 2734985Sodium chlorodifluoroacetate

Product 1

HCID 27582954-(Difluoromethoxy)-3-hydroxybenzaldehydeYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3,4-Dihydroxybenzaldehyde (20 g, 145 mmol), chlorodifluoroacetic acid sodium salt (55.19 g, 362 mmol) and sodium hydroxide (5.50 g, 138 mmol) were stirred in DMF (1200 mL) at 55° C. under nitrogen for 16 hours. The pH was adjusted to 1.0 by the addition of 10% aqueous HCl followed by extraction with ethyl acetate (3×500 mL). The combined extracts were evaporated under vacuum. The residue was purified on silica gel using a 10-20% ethyl acetate/hexane gradient. 4-difluoromethoxy-3-hydroxybenzaldehyde was isolated in 24% yield (6.62 g). 1H NMR (CDCl3, 400 MHz) δ 6.1 (br s, 1H), 6.48-6.85 (t, 1H OCHF2), 7.26 (d, 1H), 7.44 (d, 1H), 7.55 (s, 1H), 9.91 (s, 1H).

Workup

  1. extractionfollowed by extraction with ethyl acetate (3×500 mL)
  2. customThe combined extracts were evaporated under vacuum
  3. customThe residue was purified on silica gel using a 10-20% ethyl acetate/hexane gradient

Sources & evidence

ORD record
ord-8cb73ad33eca4bcaa8b8fdbddd507143
Source dataset
uspto-grants-2007_06
Patent number
US07226930B2

Reaction notes

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