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

HRID 746772ノート

反応式

HRID 746772 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-374913e2d2124f568aef7b534fee3bc3
出典データセット
uspto-grants-2008_07
特許番号
US07393868B2

反応ノート

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