Benzonitrile → 5-Methyl-3,6-diphenyl-5H-isoxazolo[4,3-c]pyridin-4-one

HRID 8310

Reaction equation

HRID 8310 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([CH3:16])=[N:7][O:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:4].C([Li])CCC.[C:22](#N)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1>[CH3:1][N:2]1[C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:16][C:6]2=[N:7][O:8][C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[C:5]2[C:3]1=[O:4]

Participants

5

Reactant 3

HCID 7505BenzonitrileHCID 666631943-Methyl-5-phenyl-isoxazole-4-carboxylic acid methylamideHCID 178418339Butyllithium

Product 1

HCID 220155655-Methyl-3,6-diphenyl-5H-isoxazolo[4,3-c]pyridin-4-oneYield 48.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

159 mg (0.73 mmol) of 3-methyl-5-phenyl-isoxazole-4-carboxylic acid methylamide is suspended in 4 ml of THF under argon. At −5° C. a solution of butyl lithium (1.0 ml, 1.6M in hexane, 1.6 mmol, 2.2 eq.) is slowly added. After 1 h at this temperature, the solution is warmed to 0° C. and 0.92 ml (0.88 mmol, 1.2 eq.) of benzonitrile is slowly added. Under warming to room temperature, the red solution is stirred for another 2 h, then quenched with 0.1 ml of water and concentrated. The residue is then taken up in 4 ml of a 4M solution of HCl in dioxane and the suspension stirred for 16 h at room temperature. Then, the solvent is removed and the residue dissolved in ethyl acetate and carefully neutralised with sat. NaHCO3-solution. The phases are separated and the organic phases washed with brine, dried over Na2SO4 and concentrated. Chromatographic purification (hexane/ethyl acetate 90:10) yields 108 mg (48%) of 5-methyl-3,6-diphenyl-5H-isoxazolo[4,3-c]pyridin-4-one as a white solid. Mass spectrum: m/z (M+H)+: 303.2

Workup

  1. temperatureUnder warming to room temperature
  2. customquenched with 0.1 ml of water
  3. concentrationconcentrated
  4. stirringthe suspension stirred for 16 h at room temperature
  5. customThen, the solvent is removed
  6. dissolutionthe residue dissolved in ethyl acetate
  7. customThe phases are separated
  8. washthe organic phases washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customChromatographic purification (hexane/ethyl acetate 90:10)

Sources & evidence

ORD record
ord-0e553ab04cd04660a202ef9b4f2450c0
Source dataset
uspto-grants-2006_08
Patent number
US07087756B2

Linked notes

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