Hydrochloric Acid → 5-Fluoro-3-methoxy-2-nitrophenol

HRID 515197Notes

Reaction equation

HRID 515197 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[N+:11]([O-:13])=[O:12].[OH-:14].[Na+].Cl>CS(C)=O.O>[F:8][C:6]1[CH:5]=[C:4]([O:9][CH3:10])[C:3]([N+:11]([O-:13])=[O:12])=[C:2]([OH:14])[CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 103301291,5-Difluoro-3-methoxy-2-nitrobenzene

Product 1

HCID 184333835-Fluoro-3-methoxy-2-nitrophenolYield 60%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1,5-difluoro-3-methoxy-2-nitro-benzene (20 g, 105 mmol) in dimethylsulfoxide (50 ml) is added a 10N aqueous solution of sodium hydroxide (31.5 ml) and the mixture is stirred at room temperature for 18 h and at 60° C. for 3 h. After completion of reaction (monitored by TLC), the mixture is diluted with water (50 ml), acidified with 2N hydrochloric acid to pH 3 and extracted with ethyl acetate (3×100 ml). The combined organic layers are washed with water (50 ml), brine (50 ml), dried over sodium sulfate and concentrated in vacuo. The crude product is purified by flash column chromatography (15% ethyl acetate/hexane) to yield 5-fluoro-3-methoxy-2-nitro-phenol (12.0 g, 63.5 mmol, 60%).

Workup

  1. customAfter completion of reaction (monitored by TLC)
  2. extractionextracted with ethyl acetate (3×100 ml)
  3. washThe combined organic layers are washed with water (50 ml), brine (50 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by flash column chromatography (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-37f261af25fb415e93533fd218ec58cc
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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