Indole → N-(4-methylphenyl)indole

HRID 1832240Notes

Reaction equation

HRID 1832240 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.I[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O.O.[Cu]>[CH3:17][C:14]1[CH:15]=[CH:16][C:11]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 798IndoleHCID 11430Potassium CarbonateHCID 122074-Iodotoluene

Product 1

HCID 9794286N-(4-methylphenyl)indoleYield 79.1%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-H-indole (58.5 mg, 0.500 mmol), 1-iodo-4-methylbenzene (0.218 g, 1.00 mmol), copper powder (32.0 mg, 0.500 mmol), and K2CO3 (0.138 g, 1.00 mmol) in 1-methyl-2-pyrrolidinone (1.00 mL) was heated at 150° C. for 12 h under argon. The resulting mixture was diluted with H2O (6 mL). The aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by preparative TLC using EtOAc:hexane (1:4) to give the desired product (82.0 mg, 79.0%): 1H NMR (400 MHz, CDCl3) δ 7.67 (d, 1H, J=7.7 Hz), 7.52 (d, 1H, J=7.4 Hz), 7.38 (d, 2H, J=8.4 Hz), 7.34–7.29 (m, 3H), 7.21 (t, 1H, J=7.0 Hz), 7.15 (t, 1H, J=7.0 Hz), 6.66 (d, 1H, J=3.3 Hz), 2.43 (s, 3H); ESMS m/e: 208.0 (M+H)+.

Workup

  1. extractionThe aqueous layer was extracted with CH2Cl2 (3×10 mL)
  2. washThe combined organic extracts were washed with brine (10 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-a043f8d6cd144e3b856ee63ee55ad200
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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