Cyclohexene → Ethyl 5-amino-1H-indole-2-carboxylate

HRID 1484022Notes

Reaction equation

HRID 1484022 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([N+:15]([O-])=O)=[CH:10][CH:9]=2)=[O:5])[CH3:2].C1CCCCC=1>C1COCC1.CO.[OH-].[OH-].[Pd+2]>[NH2:15][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:14]2

Participants

5

Reactant 2

HCID 8079CyclohexeneHCID 280312Ethyl 5-nitro-1H-indole-2-carboxylate

Product 1

HCID 10726872Ethyl 5-amino-1H-indole-2-carboxylateYield 85.8%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of 5-Nitro-1H-indole-2-carboxylic acid ethyl ester 15 (88.7 mg, 0.38 mmol) and cyclohexene (0.1 mL, 0.98 mmol) in THF/MeOH (3/8 mL) in the presence of Pd(OH)2 on activated carbon (Pearlman's catalyst) (2.74 g) was heated to reflux for 5 h. The reaction mixture was cooled to room temperature. The mixture was filtered through a pad of Celite. The Celite and the palladium were washed with EtOAc. The combined solution was concentrated. The residue was purified by flash column chromatography on silica gel, eluting with 5-45% EtOAc/hexane to afford 66.6 mg of ethyl 5-amino-1H-indole 2-carboxylate 20. 1H-NMR (CDCl3): 8.653 (Br, 1H, NH), 7.228 (d, J=8.5-9.0 Hz, 1H, Ar—H), 7.031 (dd, J=1.0 Hz and 2.0 Hz, 1H, Ar—H), 6.932 (d, J=2.5 Hz, 1H, Ar—H), 6.803 (dd, J=2.5 Hz, 1H, Ar—H), 4.379 (q, J=7.0-7.5 Hz, 2H, CH2), 1.396 (t, J=7.0-7.5 Hz, 3H, CH3). LC-MS: 205.2 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 h
  3. filtrationThe mixture was filtered through a pad of Celite
  4. washThe Celite and the palladium were washed with EtOAc
  5. concentrationThe combined solution was concentrated
  6. customThe residue was purified by flash column chromatography on silica gel
  7. washeluting with 5-45% EtOAc/hexane

Sources & evidence

ORD record
ord-6af6be9f38124c0ab5d393b1d056165f
Source dataset
uspto-grants-2016_08
Patent number
US09421204B2

Reaction notes

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