Sodium Hydroxide → 3-Methylbenzo[d]isoxazole-5-carbonitrile

HRID 398359Notes

Reaction equation

HRID 398359 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6](F)=[C:7]([C:9](=O)[CH3:10])[CH:8]=1)#[N:2].Cl.[OH:14][NH2:15].[OH-].[Na+]>CO.CN(C=O)C.[Cl-].[Na+].O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:14][N:15]=[C:9]([CH3:10])[C:7]=2[CH:8]=1)#[N:2]

Participants

7

Reactant 3

HCID 14798Sodium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 230002093-Acetyl-4-fluorobenzonitrile

Product 1

HCID 230002453-Methylbenzo[d]isoxazole-5-carbonitrile

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 5′-cyano-2′-fluoroacetophenone (500 mg, 3.06 mmol) in MeOH (5 mL) was added hydroxyamine HCl salt (223 mg, 3.22 mmol) and sodium hydroxide (129 mg, 3.22 mmol). The reaction mixture was stirred at room temperature for 0.5 h and concentrated in vacuo to afford a solid product. This solid was added to a suspension of sodium hydroxide (147 mg, 3.68 mmol) in DMF (5 mL) at 0° C. After 0.5 h the reaction mixture was warmed to room temperature for 4 h and poured into cold brine. The mixture was extracted with ethyl acetate, the organic layer was dried over MgSO4, and concentrated in vacuo to provide a residue. Purification via flash column chromatography (15×150 mm column; gradient elution with MeOH:CH2Cl2:CH2Cl2 saturated with NH3, 5:65:30 to 10:60:30 300 mL each) afforded of a solid:

Workup

  1. concentrationconcentrated in vacuo
  2. customto afford a solid product
  3. temperatureAfter 0.5 h the reaction mixture was warmed to room temperature for 4 h
  4. extractionThe mixture was extracted with ethyl acetate
  5. dry with materialthe organic layer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto provide a residue
  8. customPurification
  9. washvia flash column chromatography (15×150 mm column; gradient elution with MeOH:CH2Cl2:CH2Cl2 saturated with NH3, 5:65:30 to 10:60:30 300 mL each)
  10. customafforded of a solid

Sources & evidence

ORD record
ord-c377dad437b7499aabf775b45401c9b5
Source dataset
uspto-grants-2003_08
Patent number
US06610692B1

Reaction notes

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