Indole → 1-(pyridin-3-yl)-1H-indole

HRID 1678128Notes

Reaction equation

HRID 1678128 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CCOCC>[N:3]1[CH:4]=[CH:5][CH:6]=[C:7]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)[CH:2]=1

Participants

7

Reactant 4

HCID 798IndoleHCID 79732-BromopyridineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 134903481-(pyridin-3-yl)-1H-indoleYield 15%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

Under an argon atmosphere, a solution of bromopyridine (1.7 mL, 17.6 mmol) in toluene (15 mL) is added to indole (2.0 g, 17.1 mmol), tris(dibenzylideneacetone)palladium (480 mg, 0.52 mmol), 2-(di-tert-butylphosphino)biphenyl (5.52 mg, 0.76 mmol), sodium tert-butoxide and toluene (25 mL) and the stirred mixture is heated at 100° C. for 48 hr. After cooling to room temperature, ether is added and the reaction mixture is filtered through Hi-Flo and concentrated. The residue is purified by chromatography eluting with pentane-25% ethyl acetate. Product containing fractions are combined and concentrated to afford 1-(pyridin-3-yl)-1H-indole (485 mg, 15%) as a yellow-brown oil.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe reaction mixture is filtered through Hi-Flo
  3. concentrationconcentrated
  4. customThe residue is purified by chromatography
  5. washeluting with pentane-25% ethyl acetate
  6. additionProduct containing fractions
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ad105c07449141219d45c1e9f2688519
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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