Sodium Carbonate → 5-(piperazin-1-yl)-1H-indole

HRID 1647398Notes

Reaction equation

HRID 1647398 reaction equation
Cl.Cl[CH2:3][CH2:4][NH:5][CH2:6][CH2:7]Cl.[NH2:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[CH:13]2.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[NH:15]1[C:16]2[C:12](=[CH:11][C:10]([N:9]3[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]3)=[CH:18][CH:17]=2)[CH:13]=[CH:14]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 788675-AminoindoleHCID 522769Bis(2-chloroethyl)amine hydrochloride

Product 1

HCID 221748205-(piperazin-1-yl)-1H-indoleYield 18.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Bis(2-chloroethyl)amine hydrochloride (3.60 g, 20.2 mmol) was added to a suspension of 5-aminoindole (2.53 g, 19.1 mmol) in ethanol (30 ml) and the mixture heated at reflux for 16 h. The mixture was allowed to cool, sodium carbonate (2.14 g, 20.2 mmol) was added and the reaction mixture heated at reflux for 8 h. The mixture was allowed to cool, filtered and the filtrate evaporated. The residue was dissolved in 1M hydrochloric acid (100 ml) and extracted with dichloromethane (2×50 ml). The aqueous phase was made basic with 4M sodium hydroxide (30 ml) and extracted with ethyl acetate (2×100ml). The extracts were washed with brine (100 ml), combined and dried (MgSO4). The residue from evaporation of the extracts was purified by flash chromatography, eluting with dichloromethane/methanol/ammonia, to give 1-(5-indolyl)piperazine (0.71 g, 18%), as a cream solid; δH (DMSO-d6) 2.94 (4H, m, 2×piperzinyl CH2), 3.00 (4H, m, 2×piperazinyl CH2), 6.29 (1H, m, 3-H), 6.84 (1H, dd, J 9.0,2.0 Hz, 6-H), 7.00 (1H, d, J 2.0 Hz, 2-H), 7.24 (2H, m, 4-H, 7-H), and 10.82 (1H, br s, NH).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 16 h
  3. temperatureto cool
  4. temperaturethe reaction mixture heated
  5. temperatureat reflux for 8 h
  6. temperatureto cool
  7. filtrationfiltered
  8. customthe filtrate evaporated
  9. dissolutionThe residue was dissolved in 1M hydrochloric acid (100 ml)
  10. extractionextracted with dichloromethane (2×50 ml)
  11. extractionextracted with ethyl acetate (2×100ml)
  12. washThe extracts were washed with brine (100 ml)
  13. dry with materialdried (MgSO4)
  14. customThe residue from evaporation of the extracts
  15. customwas purified by flash chromatography
  16. washeluting with dichloromethane/methanol/ammonia

Sources & evidence

ORD record
ord-45b540cf948f473d987f7d4ecbbd9dae
Source dataset
uspto-grants-1995_07
Patent number
US05432177

Reaction notes

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