Hydrochloric Acid → Methyl 3-(difluoromethoxy)-2,4-difluorobenzoate

HRID 377272Notes

Reaction equation

HRID 377272 reaction equation
[F:1][C:2]1[C:11]([OH:12])=[C:10]([F:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(=O)([O-])[O-].[K+].[K+].Cl[CH:21]([F:23])[F:22].Cl>CN(C)C=O.O.C(OCC)(=O)C>[F:1][C:2]1[C:11]([O:12][CH:21]([F:23])[F:22])=[C:10]([F:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6372ChlorodifluoromethaneHCID 11430Potassium CarbonateHCID 19358310Methyl 2,4-difluoro-3-hydroxybenzoate

Product 1

HCID 19358353Methyl 3-(difluoromethoxy)-2,4-difluorobenzoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

In 20 ml of N,N-dimethylformamide was dissolved 1.00 g of methyl 2,4-difluoro-3-hydroxy-benzoate, followed by adding thereto 0.88 g of potassium carbonate and then 12 ml of a 6 M solution of chlorodifluoromethane in N,N-dimethylformamide, and the resulting mixture was stirred in a sealed tube at 120-130° C. for 2.5 hours. The reaction mixture was added to a mixed solvent of 100 ml of ethyl acetate and 200 ml of water and the pH was adjusted to 2 with 6N hydrochloric acid, after which the organic layer was separated. The organic layer obtained was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent. The resulting residue was purified by a column chromatography (eluent; n-hexane:ethyl acetate=4:1) to obtain 1.02 g of methyl 2,4-difluoro-3-difluoromethoxybenzoate as colorless crystals.

Workup

  1. additionby adding
  2. customafter which the organic layer was separated
  3. customThe organic layer obtained
  4. washwas washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customThe resulting residue was purified by a column chromatography (eluent; n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-91844c6e9a644a9c9817ac290749d05d
Source dataset
uspto-grants-2000_02
Patent number
US06025370

Reaction notes

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