Acetic Anhydride → 5-Methyl-1H-indole-3-carbonitrile

HRID 1604623Notes

Reaction equation

HRID 1604623 reaction equation
[CH:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[NH:5][CH:4]=1)=O.Cl.[NH2:14]O.C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>C(O)(=O)C>[C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[NH:5][CH:4]=1)#[N:14]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 2591875-Methylindole-3-carboxaldehydeHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium Acetate

Product 1

HCID 196037315-Methyl-1H-indole-3-carbonitrileYield 22.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 3-formyl-5-methylindole (0.50 g), hydroxylamine hydrochloride (0.44 g) and sodium acetate (0.52 g) in acetic acid (5 ml) was stirred for 2 hours, then acetic anhydride (2.5 ml) was added to the mixture and allowed to react under reflux for 0.5 hour. After cooling, the reaction mixture was poured into ice-water and extracted with ethyl acetate. After filtration of insoluble materials, the filtrate was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was subjected to column chromatography on silica gel and eluted with a mixture of ethyl acetate and chloroform. The fractions containing the objective compounds were combined and concentrated under reduced pressure to give 3-cyano-5-methylindole (109 mg).

Workup

  1. customto react
  2. temperatureunder reflux for 0.5 hour
  3. temperatureAfter cooling
  4. extractionextracted with ethyl acetate
  5. filtrationAfter filtration of insoluble materials
  6. washthe filtrate was washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated under reduced pressure
  9. washeluted with a mixture of ethyl acetate and chloroform
  10. additionThe fractions containing the objective compounds
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-73dd3509f3ba495fadf7846ef73e1851
Source dataset
uspto-grants-1999_11
Patent number
US05994378

Reaction notes

Loading…