Oxalyl chloride → 1-(Indole-5-carbonyl)-4-phenethylpiperazine

HRID 1086854Notes

Reaction equation

HRID 1086854 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([OH:12])=O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C(Cl)(=O)C(Cl)=O.[CH2:19]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(C(C)C)CC)(C)C>C1COCC1.CN(C=O)C.ClCCl>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([N:30]3[CH2:31][CH2:32][N:27]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:28][CH2:29]3)=[O:12])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 742801H-Indole-5-Carboxylic AcidHCID 792141-PhenethylpiperazineHCID 81531Diisopropylethylamine

Product 1

HCID 149859971-(Indole-5-carbonyl)-4-phenethylpiperazine

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Indole-5-carboxylic acid (57 mg, 0.35 mmol) was dissolved in THF(2 ml) and DMF (1 drop), then oxalyl chloride (37 μl, 54 mg, 0.42 mmol) was added. The mixture was stirred at room temperature for 3 hours, the solvent was evaporated under reduced pressure and the residue was dissolved in DMF (2 ml) and added to a stirred solution of 1-phenethylpiperazine (66 mg, 0.35 mmol) and diisopropylethylamine (91 μl, 68 mg, 0.52 mmol) in dichloromethane (1 ml). The mixture was stirred at room temperature for 24 hours, then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /CH3OH/NH3 ; 95:5:0.5 and crystallized from EtOAc/hexane to give the piperazine as microcrystals (32 mg, 27%), mp 105°-108° C. δH (CDCl3) 8.47(1H, br s), 7.73(1H, s), 7.38(1H, d J 8.4 Hz), 7.32-7.19(7H, m), 6.56(1H, br s), 3.7(4H, br s), 2.81(2H, m), 2.65(2H, m), and 2.6(4H, br s).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (2 ml)
  3. stirringThe mixture was stirred at room temperature for 24 hours
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with CH2Cl2 /CH3OH/NH3
  7. custom95:5:0.5 and crystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-c62a4b98bde34dbd84a8225a42a4089e
Source dataset
uspto-grants-1991_07
Patent number
US05032598

Reaction notes

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