Diisopropylethylamine → 2-(4-Methyl-piperazin-1-yl)ethyl 4-(4-methoxyphenyl)piperazine-1-carboxylate

HRID 417975Notes

Reaction equation

HRID 417975 reaction equation
[C:1](=[O:22])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.CCN(C(C)C)C(C)C.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([N:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)=[CH:36][CH:35]=1>CN(C=O)C>[CH3:32][O:33][C:34]1[CH:35]=[CH:36][C:37]([N:40]2[CH2:45][CH2:44][N:43]([C:1]([O:2][CH2:3][CH2:4][N:5]3[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]3)=[O:22])[CH2:42][CH2:41]2)=[CH:38][CH:39]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2697221-(4-Methoxyphenyl)piperazineHCID 574450072-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate2×

Product 1

HCID 426357962-(4-Methyl-piperazin-1-yl)ethyl 4-(4-methoxyphenyl)piperazine-1-carboxylateYield 17.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 680 mg, 2.2 mmol) was dissolved in DMF (20 mL). DIPEA (0.76 mL, 4.4 mmol) and 4-(4-methoxyphenyl)piperazine (422 mg, 2.2 mmol) were added and the reaction mixture was stirred at room temperature for 24 hours, and the reaction mixture was then concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 500:8:1 mixture of DCM:EtOH:NH3, followed by a 50:8:1 mixture of DCM:EtOH:NH3). The residue was recrystallised from EtOAc to give 2-(4-methyl-piperazin-1-yl)ethyl 4-(4-methoxyphenyl)piperazine-1-carboxylate (137 mg, 17%) as a white solid.

Workup

  1. concentrationthe reaction mixture was then concentrated in vacuo
  2. customThe residue was purified by normal phase column chromatography (
  3. washeluting with DCM
  4. additionfollowed by a 500:8:1 mixture of DCM
  5. additionEtOH:NH3, followed by a 50:8:1 mixture of DCM
  6. customThe residue was recrystallised from EtOAc

Sources & evidence

ORD record
ord-4ad1924324954db0ae1cccaf247fd855
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

Loading…