1-(3-(Trifluoromethyl)phenyl)piperazine → 2-(4-Methylpiperazin-1-yl)ethyl 4-(3-trifluoromethyl-phenyl)piperazine-1-carboxylate

HRID 417970

Reaction equation

HRID 417970 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.[F:30][C:31]([F:45])([F:44])[C:32]1[CH:33]=[C:34]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:35]=[CH:36][CH:37]=1>CN(C=O)C>[NH3:5].[F:45][C:31]([F:30])([F:44])[C:32]1[CH:33]=[C:34]([N:38]2[CH2:43][CH2:42][N:41]([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])[CH2:40][CH2:39]2)[CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 42961-(3-(Trifluoromethyl)phenyl)piperazineHCID 8471TriethylamineHCID 574450072-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate2×

Product 2

HCID 222AmmoniaHCID 426356232-(4-Methylpiperazin-1-yl)ethyl 4-(3-trifluoromethyl-phenyl)piperazine-1-carboxylateYield 126.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 761 mg, 2.5 mmol) was dissolved in DMF (20 mL). NEt3 (0.4 mL, 2.9 mmol) and 4-(3-trifluoromethyl-phenyl)piperazine (583 mg, 2.5 mmol) were added and the reaction mixture was stirred at room temperature for 24 hours, the reaction mixture was then concentrated in vacuo. The resulting residue was dissolved in EtOAc (50 mL) and washed with 1 M 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 100:8:1 mixture of DCM:EtOH:NH3) to give 2-(4-methylpiperazin-1-yl)ethyl 4-(3-trifluoromethyl-phenyl)piperazine-1-carboxylate (631 mg, 64%) as a colourless oil.

Workup

  1. concentrationthe reaction mixture was then concentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in EtOAc (50 mL)
  3. washwashed with 1 M 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 100:8:1 mixture of DCM

Sources & evidence

ORD record
ord-8139c60e46dd481ba056a1403dd7669b
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Linked notes

Loading…