Dimedone → 6,6-Dimethyl-1,5,6,7-tetrahydro-4H-indol-4-one

HRID 1937627Notes

Reaction equation

HRID 1937627 reaction equation
[CH3:1][C:2]1([CH3:10])[CH2:7][C:6](=[O:8])[CH2:5][C:4](=O)[CH2:3]1.CO[CH:13](OC)[CH2:14][NH2:15].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:10][C:2]1([CH3:1])[CH2:3][C:4]2[NH:15][CH:14]=[CH:13][C:5]=2[C:6](=[O:8])[CH2:7]1

Participants

5

Reactant 3

HCID 31358DimedoneHCID 89728Aminoacetaldehyde dimethyl acetalHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 27522846,6-Dimethyl-1,5,6,7-tetrahydro-4H-indol-4-oneYield 5.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 5,5-dimethyl-1,3-cyclohexandione (30 g, 0.21 mol), aminoacetaldehyde dimethyl acetal (35 mL, 0.32 mol) and p-toluenesulphonic acid hydrate (1.5 g, 8 mmol) in toluene (250 mL) were heated at reflux for 4 h using Dean-Stark apparatus to remove the water. The toluene was evaporated and the residue dissolved in 3N HCl (250 mL). The solution was heated at 60° C. for 6 h. After this time the mixture was cooled to room temperature and extracted with DCM (6×). The combined organic layers were dried (MgSO4), evaporated and the residue chromatographed on silica gel, eluting with isohexane: EtOAc (4:1→1:1). The fractions containing the desired product were combined, evaporated and the residue triturated with ether. The title compound (1.8 g, 5%) was isolated as a cream solid. mp 177-178° C. 1H NMR (360 MHz, d6-DMSO) 8 1.02 (6H,s), 2.19 (2H,s), 2.63 (2H,s), 6.23 (1H,t, J=3.9 Hz), 6.71 (1H,t, J=3.9 Hz). MS (ES+) 164 (M+1).

Workup

  1. temperatureat reflux for 4 h
  2. customto remove the water
  3. customThe toluene was evaporated
  4. dissolutionthe residue dissolved in 3N HCl (250 mL)
  5. temperatureAfter this time the mixture was cooled to room temperature
  6. extractionextracted with DCM (6×)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. customevaporated
  9. customthe residue chromatographed on silica gel
  10. washeluting with isohexane: EtOAc (4:1→1:1)
  11. additionThe fractions containing the desired product
  12. customevaporated
  13. customthe residue triturated with ether

Sources & evidence

ORD record
ord-749df1ea118149fbb2192e225a36cd3a
Source dataset
uspto-grants-2002_05
Patent number
US06395766B1

Reaction notes

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