Hydroxyamine hydrochloride → 6-Bromo-2,4-difluoro-3-methoxy-benzonitrile

HRID 746772Notes

Reaction equation

HRID 746772 reaction equation
Cl.NO.[Br:4][C:5]1[C:10]([CH:11]=O)=[C:9]([F:13])[C:8]([O:14][CH3:15])=[C:7]([F:16])[CH:6]=1.CC[N+:19](S(N=C(OC)[O-])(=O)=O)(CC)CC>CN(C=O)C>[Br:4][C:5]1[C:10]([C:11]#[N:19])=[C:9]([F:13])[C:8]([O:14][CH3:15])=[C:7]([F:16])[CH:6]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 866131686-Bromo-2,4-difluoro-3-methoxybenzaldehyde

Product 1

HCID 866131696-Bromo-2,4-difluoro-3-methoxy-benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

Add hydroxylamine hydrochloride (608 mg, 8.8 mmol) to a solution of 6-Bromo-2,4-difluoro-3-methoxy-benzaldehyde (2.0 g, 7.96 mmol) in anhydrous DMF (4 ml). Heat the mixture to 150° C. for 2 h. Add water to the cooled mixture and extract the product with EtOAc (×2). Wash the combined organic layers with water (×3), saturated aq. sodium chloride and dry over anhydrous sodium sulfate. Filter and concentrate. Dissolve the concentrate in anhydrous THF and add 3 equivalent of the Burgess reagent ((methoxycarbonylsulfamoyl)triethylammonium hydroxide, inner salt). Heat the mixture under reflux under nitrogen atmosphere overnight. Concentrate to yield a crude residue. Purification by flash chromatography (Silica gel-hexane/EtOAc) yields the title compound.

Workup

  1. extractionAdd water to the cooled mixture and extract the product with EtOAc (×2)
  2. washWash the combined organic layers with water (×3), saturated aq. sodium chloride
  3. dry with materialdry over anhydrous sodium sulfate
  4. filtrationFilter
  5. concentrationconcentrate
  6. dissolutionDissolve the
  7. concentrationconcentrate in anhydrous THF
  8. temperatureHeat the mixture
  9. temperatureunder reflux under nitrogen atmosphere overnight
  10. concentrationConcentrate
  11. customto yield a crude residue
  12. customPurification by flash chromatography (Silica gel-hexane/EtOAc)

Sources & evidence

ORD record
ord-374913e2d2124f568aef7b534fee3bc3
Source dataset
uspto-grants-2008_07
Patent number
US07393868B2

Reaction notes

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