5-(2,2-Dimethyl-propyl)-isoxazole-3-carboxylic acid tert-butylamide → 5-(2,2-Dimethyl-propyl)isoxazole-3-carbonitrile

HRID 1664233Notes

Reaction equation

HRID 1664233 reaction equation
C([NH:5][C:6]([C:8]1[CH:12]=[C:11]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[O:10][N:9]=1)=O)(C)(C)C.O(Cl)Cl.[P+3]>>[CH3:15][C:14]([CH3:17])([CH3:16])[CH2:13][C:11]1[O:10][N:9]=[C:8]([C:6]#[N:5])[CH:12]=1

Participants

3

Reactant 2

HCID 674406745-(2,2-Dimethyl-propyl)-isoxazole-3-carboxylic acid tert-butylamideHCID 178479710HCID 178479710, compound

Product 1

HCID 666495545-(2,2-Dimethyl-propyl)isoxazole-3-carbonitrile

Procedure

A mixture of 5-(2,2-dimethyl-propyl)-isoxazole-3-carboxylic acid tert-butylamide (58.0 g, 0.243 mol) and phosphorus (III) oxychloride (156 ml, 1.70 mol) is heated under nitrogen atmosphere at reflux temperature for 2 h. The reaction mixture is cooled to rt and concentrated to remove excess phosphorus (III) oxychloride. The residue is diluted with DCM (2000 ml) and washed with saturated aq sodium bicarbonate (500 ml×2). The organic layer is washed with brine, dried over sodium sulfate, and concentrated. The residue is purified by chromatography on silica (DCM/hexanes 1/1) to yield the target compound as yellow liquid.

Workup

  1. temperatureis heated under nitrogen atmosphere
  2. temperatureat reflux temperature for 2 h
  3. concentrationconcentrated
  4. customto remove excess phosphorus (III) oxychloride
  5. additionThe residue is diluted with DCM (2000 ml)
  6. washwashed with saturated aq sodium bicarbonate (500 ml×2)
  7. washThe organic layer is washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue is purified by chromatography on silica (DCM/hexanes 1/1)

Sources & evidence

ORD record
ord-4f8844ce87a54bba94c3c8cd41a6e3d7
Source dataset
uspto-grants-2011_10
Patent number
US08039455B2

Reaction notes

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