Water → 4-Chloro-2-fluoro-5-(2,2-difluorocyclopropylmethoxy)nitrobenzene

HRID 1722921Notes

Reaction equation

HRID 1722921 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[OH:12].C(=O)([O-])[O-].[K+].[K+].[F:19][C:20]1([F:25])[CH2:22][CH:21]1[CH2:23]Br.O>CN(C)C=O>[Cl:1][C:2]1[C:3]([O:12][CH2:23][CH:21]2[CH2:22][C:20]2([F:25])[F:19])=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 158655Phenol, 2-chloro-4-fluoro-5-nitro-HCID 27614022-(Bromomethyl)-1,1-difluorocyclopropane

Product 1

HCID 141294314-Chloro-2-fluoro-5-(2,2-difluorocyclopropylmethoxy)nitrobenzene

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.6 g 2-Chloro-4-fluoro-5-nitrophenol was dissolved in dimethylformamide and treated with potassium carbonate. The mixture was stirred at room temperature for one hour and then 3.3 g 2,2-difluorocyclopropylmethyl bromide added. It was the heated at 80° C. for 2 hours and added to water. The mixture was extracted with methylene chloride and the organic phase washed with saturated brine, dried over magnesium sulphate and concentrated. The residue was chromatographed on silica gel using a mixture of 3 parts hexane and 1 part ethyl acetate. There was obtained 5 g (=93% of theory) of yellow crystals whose nmr spectrum is as follows: δ=1.1-2.4 ppm (m) 3H, δ=4.15 ppm (d 7 Hz,tr 1.5 Hz) 2H, δ=7.35 ppm (d 10 Hz) 1H, δ=7.5 ppm (d 7 Hz) 1H.

Workup

  1. temperatureheated at 80° C. for 2 hours
  2. extractionThe mixture was extracted with methylene chloride
  3. washthe organic phase washed with saturated brine
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel using
  7. additiona mixture of 3 parts hexane and 1 part ethyl acetate
  8. customThere was obtained 5 g (=93% of theory) of yellow crystals whose nmr spectrum

Sources & evidence

ORD record
ord-0f2e047be0434378acb8cf00e7bd41a0
Source dataset
uspto-grants-1989_08
Patent number
US04859230

Reaction notes

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