Acetic Acid → 3-methyl-4,5,6,7-tetrahydro-1H-indol-4-one

HRID 2228617

Reaction equation

HRID 2228617 reaction equation
[CH3:1][C:2](/[CH:4]=[N:5]/O)=O.[C:7]1(=[O:14])[CH2:12][CH2:11][CH2:10][C:9](=O)[CH2:8]1.C(O)(=O)C.[OH-].[K+]>[Zn].O>[CH3:1][C:2]1[C:8]2[C:7](=[O:14])[CH2:12][CH2:11][CH2:10][C:9]=2[NH:5][CH:4]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 104341,3-CyclohexanedioneHCID 14797Potassium HydroxideHCID 6399095Isonitrosoacetone

Product 1

HCID 43573803-methyl-4,5,6,7-tetrahydro-1H-indol-4-oneYield 46%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Procedure

The subtitle compound was prepared according to the literature procedure (Hauptmann, S. et al., Z. Chem., 1966, 3, 107. Ravina, E. et al., Bio. Med. Chem. Lett., 1995, 5, 579.). A mixture of anti-pyruvic aldehyde 1-oxime (1.3 g, 15 mmol), 1,3-cyclohexanedione (1.7 g, 15 mmol), glacial acetic acid (12 mL) and water (3.0 mL) was stirred vigorously at room temperature. Zinc dust (3 g) was added slowly keeping the temperature below 60° C. After addition, this resulting brown solution was heated under reflux temperature for 2 hours. After cooling, the reaction mixture was basified by an addition of 1 M aqueous KOH. The whole was extracted with CH2Cl2 (50 mL×3), and the combined organic layers were dried over MgSO4, and concentrated in vaciio. The residue was purified by flash chromatography eluting with hexane-ethyl acetate (3:1→EtOAc only) to afford the subtitle compound (1.0 g, 46% yield) of as a yellow solid.

Workup

  1. customThe subtitle compound was prepared
  2. customthe temperature below 60° C
  3. additionAfter addition
  4. temperaturethis resulting brown solution was heated
  5. temperatureunder reflux temperature for 2 hours
  6. temperatureAfter cooling
  7. extractionThe whole was extracted with CH2Cl2 (50 mL×3)
  8. dry with materialthe combined organic layers were dried over MgSO4
  9. concentrationconcentrated in vaciio
  10. customThe residue was purified by flash chromatography
  11. washeluting with hexane-ethyl acetate (3:1→EtOAc only)

Sources & evidence

ORD record
ord-3bc59f1b2f7f4126b36500386b5af305
Source dataset
uspto-grants-2002_07
Patent number
US06417202B1

Linked notes

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