3,5,5-Trimethyl-4-oxo-4,5,6,7-tetrahydroindole-2-carboxylic acid benzyl ester → 3,5,5-Trimethyl-4-oxo-4,5,6,7-tetrahydroindole

HRID 1751974Notes

Reaction equation

HRID 1751974 reaction equation
C(OC([C:11]1[NH:12][C:13]2[CH2:14][CH2:15][C:16]([CH3:23])([CH3:22])[C:17](=[O:21])[C:18]=2[C:19]=1[CH3:20])=O)C1C=CC=CC=1.[H][H]>C(OCC)(=O)C.CO.[Pd]>[CH3:20][C:19]1[C:18]2[C:17](=[O:21])[C:16]([CH3:23])([CH3:22])[CH2:15][CH2:14][C:13]=2[NH:12][CH:11]=1

Participants

6

Reactant 2

HCID 674199773,5,5-Trimethyl-4-oxo-4,5,6,7-tetrahydroindole-2-carboxylic acid benzyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 184707113,5,5-Trimethyl-4-oxo-4,5,6,7-tetrahydroindole

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

3,5,5-trimethyl-4-oxo-4,5,6,7-tetrahydroindole-2-carboxylic acid benzyl ester from the previous step, 6.60 g (21.20 mmol) and 2.0 g of 10% Pd—C was suspended in ethyl acetate 150 mL and hydrogenated under balloon of hydrogen for 3 hours. The reaction mixture was diluted with methanol 0.5 L and the mixture was stirred under Ar for 30 min to dissolve the precipitated carboxylic acid intermediate. The catalyst was then removed by filtration and the filtrates were evaporated to dryness and dried on highvac. The residue was dissolved in trifluoroacetic acid 40 mL, the solution was stirred on a 45° C. bath for 30 min, then evaporated to dryness. The residue was dried on highvac. The crude material was applied onto a column of silica (60 g) in dichloromethane and eluted with 10:1 dichloromethane-ethyl acetate mixture. Y=3.17 g (84% overall) of 3,5,5-trimethyl-4-oxo-4,5,6,7-tetrahydroindole as a white solid that gradually turns pink on air and light. 1H-NMR (d6-DMSO, 400 MHz): 10.89 (br s, 1H), 6.44 (s, 1H), 2.72 (t, 6.3 Hz, 2H), 2.12 (s, 3H), 1.85 (t, 6.3 Hz, 2H), 1.04 (s, 6H)

Workup

  1. customThe catalyst was then removed by filtration
  2. customthe filtrates were evaporated to dryness
  3. customdried on highvac
  4. dissolutionThe residue was dissolved in trifluoroacetic acid 40 mL
  5. stirringthe solution was stirred on a 45° C. bath for 30 min
  6. customevaporated to dryness
  7. customThe residue was dried on highvac
  8. washeluted with 10:1 dichloromethane-ethyl acetate mixture

Sources & evidence

ORD record
ord-2d3070d732ae41588f2e9091c355e441
Source dataset
uspto-grants-2015_10
Patent number
US09162981B2

Reaction notes

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