Indole → 1-Ethyl-1H-indole

HRID 28416Notes

Reaction equation

HRID 28416 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:10](OCC)(=O)[C:11](OCC)=O.CC(C)([O-])C.[K+]>CN(C=O)C.O>[CH2:10]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)[CH3:11]

Participants

6

Reactant 3

HCID 798IndoleHCID 7268Diethyl OxalateHCID 23665647Potassium tert-butoxide

Product 1

HCID 2611601-Ethyl-1H-indole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of indole product in Example 38 (150 mg, 0.572 mmol) and diethyl oxalate (92 mg, 0.63 mmol) in DMF (5 mL), potassium tert-butoxide (71 mg, 0.63 mmol) was added in one portion at room temperature under nitrogen. The reaction mixture was warmed to reflux under nitrogen for 1 h and then was cooled down to room temperature. The mixture was diluted with water (50 mL) and extracted (3×) with methylene chloride. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography (SiO2, EtOAc/hexanes, 1:1) to afford the N-ethyl-indole, Example 38, (144 mg, 86%): 1H NMR (500 MHz, CDCl3) δ7.18-7.28 (m, 5H), 7.09 (d, J=3.2 Hz, 1H), 7.07 (d, J=8.5 Hz, 1H), 6.71 (d, J=8.5 Hz, 1H), 6.42 (dd, J=3.2, <1 Hz, 1H), 4.36 (t, J=8.0, 5.4 Hz, 1H), 4.12 (q, J=7.3 Hz, 2H), 4.00 (d, J=15.1 Hz, 1H), 3.85 (d, J=15.1 Hz, 1H), 3.07 (dd, J=11.3, 5.4 Hz, 1H), 2.66 (dd, J=11.3, 8.0 Hz, 1H), 2.50 (s, 3H), 1.44 (t, J=7.3 Hz, 3H).

Workup

  1. customwas added in one portion at room temperature under nitrogen
  2. temperatureThe reaction mixture was warmed
  3. temperatureto reflux under nitrogen for 1 h
  4. extractionextracted (3×) with methylene chloride
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography (SiO2, EtOAc/hexanes, 1:1)

Sources & evidence

ORD record
ord-60eab091a58d469ebcc187bc94ecdd05
Source dataset
uspto-grants-2008_09
Patent number
US07419985B2

Reaction notes

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