Ethane → 1-[beta-(2-Methyl-3-indolyl)propionyl]-4-phenylpiperazine

HRID 1580626Notes

Reaction equation

HRID 1580626 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.[Mg].C(I)C.CC.Cl[CH2:18][CH2:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24][CH2:23]1)=[O:21]>CCOCC.C(O)(=O)C.C1C=CC=CC=1>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH2:18][CH2:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:24][CH2:23]1)=[O:21])=[CH:8][CH:7]=[CH:6][CH:5]=2

Participants

9

Reactant 5

HCID 6324EthaneHCID 6340IodoethaneHCID 72242-MethylindoleHCID 2467973-Chloro-1-(4-phenylpiperazin-1-yl)propan-1-oneHCID 5462224Magnesium

Product 1

HCID 215634081-[beta-(2-Methyl-3-indolyl)propionyl]-4-phenylpiperazine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 241BenzeneSolventHCID 3283Diethyl EtherSolvent3×

Procedure

2-methylindole (26.2 g) dissolved in dry ether (100 ml) was added dropwise to the Grignard reagent prepared from 4.9 g of magnesium and 31.2 g of ethyl iodide in 100 ml of dry ether at 20°-25°C and the mixture was gently refluxed until the evolution of ethane ceased. 1-(β-Chloropropionyl)-4-phenylpiperazine (55.6 g) dissolved in dry ether (100 ml) was then slowly added to the resulting reaction mixture at a temperature below 20°C. At first the addition of the latter caused the precipitation of yellowish viscid solid, which finally became cherry-red. After the addition was completed, ether was distilled off under ordinary pressure and the viscid solid mass which remained was heated on a steam bath for 3 hours, and then cooled. The resulting reaction mixture was agitated vigorously with 250 ml of benzene and 200 ml of a 5 % aqueous solution of acetic acid. The benzene layer which was separated was washed with a 10 % aqueous solution of sodium carbonate and water, dried over anhydrous sodium sulfate and concentrated to dryness. The residual solid was recrystallized from ethanol to give 1-[β-(2-methyl-3-indolyl)propionyl]-4-phenylpiperazine, melting at 121°-122°C.

Workup

  1. additionwas then slowly added to the resulting reaction mixture at a temperature below 20°C
  2. additionAt first the addition of the latter
  3. customthe precipitation of yellowish viscid solid, which finally became cherry-red
  4. additionAfter the addition
  5. distillationether was distilled off under ordinary pressure
  6. temperaturethe viscid solid mass which remained was heated on a steam bath for 3 hours
  7. temperaturecooled
  8. customThe resulting reaction mixture
  9. customThe benzene layer which was separated
  10. washwas washed with a 10 % aqueous solution of sodium carbonate and water
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated to dryness
  13. customThe residual solid was recrystallized from ethanol

Sources & evidence

ORD record
ord-70441b3abf9d4cb899d07e0b342f6df9
Source dataset
uspto-grants-1976_01
Patent number
US03933824

Reaction notes

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