Triethylamine → 2-(4-Methylpiperazin-1-yl)-ethyl 4-(4-methylphenyl)piperazine-1-carboxylate

HRID 417972Notes

Reaction equation

HRID 417972 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(CC)CC.Cl.Cl.[CH3:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)=[CH:35][CH:34]=1>CN(C=O)C>[NH3:5].[CH3:32][C:33]1[CH:34]=[CH:35][C:36]([N:39]2[CH2:44][CH2:43][N:42]([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])[CH2:41][CH2:40]2)=[CH:37][CH:38]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 831121-(p-Tolyl)piperazine dihydrochlorideHCID 574450072-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate2×

Product 2

HCID 222AmmoniaHCID 426356262-(4-Methylpiperazin-1-yl)-ethyl 4-(4-methylphenyl)piperazine-1-carboxylateYield 60.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 866 mg, 2.8 mmol) was dissolved in DMF (25 mL). NEt3 (1.5 mL, 10.8 mmol) and 4-(4-methyl-phenyl)piperazine dihydrochloride (724 mg, 2.9 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 resulting residue was dissolved in EtOAc (50 mL) and washed with 1M aq Na2CO3 solution (5×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 200:8:1 mixture of DCM:EtOH:NH3) to give 2-(4-methylpiperazin-1-yl)-ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (293 mg, 30%) as a yellow oil.

Workup

  1. concentrationthe reaction mixture was then concentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in EtOAc (50 mL)
  3. washwashed with 1M aq Na2CO3 solution (5×50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by normal phase column chromatography (
  7. washeluting with DCM
  8. additionfollowed by a 200:8:1 mixture of DCM

Sources & evidence

ORD record
ord-e4104e0f421c4ee984101e92ab38cb83
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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