Hydrochloric Acid → 5-Chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitrophenol

HRID 1513005Notes

Reaction equation

HRID 1513005 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:12])[C:5](=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10])[OH:6].[H-].[Na+].[F:15][C:16]1[C:23]([F:24])=[CH:22][CH:21]=[C:20]([O:25][CH3:26])[C:17]=1[CH2:18]Br.Cl>CN(C)C=O.O>[Cl:1][C:2]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][C:5]([O:6][CH2:18][C:17]2[C:20]([O:25][CH3:26])=[CH:21][CH:22]=[C:23]([F:24])[C:16]=2[F:15])=[C:4]([OH:12])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 49958612,3-Difluoro-6-methoxybenzyl bromideHCID 128733644-Chloro-5-nitrocatechol

Product 1

HCID 593098495-Chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitrophenolYield 97.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 4-chloro-5-nitrocatechol (10.4 g) in N,N-dimethylformamide (55 mL) was added sodium hydride (55%, 5.04 g) under ice-cooling, and the mixture was stirred at the same temperature for 10 minutes. To the reaction mixture was added N,N-dimethylformamide (11 mL), followed by adding a solution of 2,3-difluoro-6-methoxy-benzyl bromide (14.3 g) in N,N-dimethylformamide (22 mL) under ice-cooling, and the mixture was stirred at the same temperature for 10 minutes, and then stirred at room temperature for 1.5 hours. The reaction mixture was diluted with water. The mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=7/3−1/1) to give the title compound (18.5 g).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred at the same temperature for 10 minutes
  4. stirringstirred at room temperature for 1.5 hours
  5. extractionthe resulting mixture was extracted with ethyl acetate
  6. washThe extract was washed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was removed under reduced pressure
  9. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=7/3−1/1)

Sources & evidence

ORD record
ord-5232a465ce844a38a03d462ab33565c0
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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