Indole → N,N-Diethyl-1H-indole-1-carboxamide

HRID 1920544Notes

Reaction equation

HRID 1920544 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.[CH2:12]([N:14]([CH2:18][CH3:19])[C:15](Cl)=[O:16])[CH3:13].O>C1COCC1>[CH2:12]([N:14]([CH2:18][CH3:19])[C:15]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1)=[O:16])[CH3:13]

Participants

6

Reactant 4

HCID 798IndoleHCID 962WaterHCID 6916Diethylcarbamoyl chlorideHCID 24758Sodium hydride

Product 1

HCID 11160248N,N-Diethyl-1H-indole-1-carboxamideYield 99.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (60% dispersion in mineral oil, 1.2 g, 30 mmol, 1.5 eq., Aldrich) in THF (20 mL) at 0° C. was slowly added a solution of indole (2.4 g, 20 mmol, Aldrich) in THF (20 mL). The resulting mixture was stirred at 0° C. for 20 min, after which N,N-diethylcarbamoyl chloride (2.9 mL, 22 mmol, 1.1 eq., Aldrich) was added. Then, the reaction mixture was stirred at 0° C. for 30 min. H2O (10 mL) was added to quench the reaction and the mixture was transferred to a separatory funnel. The organic and aqueous layers were separated and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried with MgSO4 and concentrated under reduced pressure. After purification of the residue by a short silica gel column (silica gel 60, 230-400 mesh) with EtOAc/hexanes as eluent, the product N,N-diethyl-1H-indole-1-carboxamide (4.3 g, 99% yield) was obtained as a light yellow oil. Further purification using flash column chromatography was deemed unnecessary. 1H NMR (400 MHz, CDCl3) δ ppm: 7.67 (d, J=8.17 Hz, 1H), 7.63 (d, J=7.65 Hz, 1H), 7.36-7.26 (m, 2H), 7.21 (t, J=7.24 Hz, 1H), 6.62 (d, J=2.77 Hz, 1H), 3.51 (q, J=7.10 Hz, 4H), 1.27 (t, J=7.11 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ ppm: 154.39, 135.51, 129.27, 125.89, 123.36, 121.55, 120.90, 112.98, 105.35, 42.41, 13.46.

Workup

  1. stirringThen, the reaction mixture was stirred at 0° C. for 30 min
  2. customto quench
  3. customthe reaction
  4. customthe mixture was transferred to a separatory funnel
  5. customThe organic and aqueous layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried with MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customAfter purification of the residue by a short silica gel column (silica gel 60, 230-400 mesh) with EtOAc/hexanes as eluent

Sources & evidence

ORD record
ord-2be51774a74541adbec14be53463f0c4
Source dataset
uspto-grants-2012_05
Patent number
US08168833B2

Reaction notes

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