1-Phenylpiperazine → HCID 66650746, compound

HRID 417981Notes

Reaction equation

HRID 417981 reaction equation
[C:1](=[O:28])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.[CH:29]1[CH:30]=[CH:31][C:32]([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)=[CH:33][CH:34]=1.CCN(CC)CC>CN(C=O)C>[C:32]1([N:35]2[CH2:40][CH2:39][N:38]([C:1]([O:2][CH2:3][CH2:4][N:5]3[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:9][CH2:10]3)=[O:28])[CH2:37][CH2:36]2)[CH:33]=[CH:34][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 70961-PhenylpiperazineHCID 8471TriethylamineHCID 66651361HCID 66651361, compound

Product 1

HCID 66650746HCID 66650746, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-(tert-Butoxycarbonyl)piperazin-1-yl)ethyl 4-nitrophenyl carbonate (7.01 g, 17.7 mmol) was dissolved in DMF (150 mL). Phenylpiperazine (2.8 mL, 18.3 mmol) and NEt3 (3.0 mL, 21.5 mmol) were added and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo, dissolved in EtOAc (250 mL), washed with 1M aq Na2CO3 solution (5×250 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by reverse phase chromatography (gradient eluting with MeOH in water, 0-100%) to give 2-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl 4-phenyl-piperazine-1-carboxylate (5.68 g, 77%) as a yellow oil. 2-(4-(tert-Butoxycarbonyl)-piperazin-1-yl)ethyl 4-phenylpiperazine-1-carboxylate (0.45 g, 1.07 mmol) was dissolved in a mixture of DCM (30 mL) and 2M HCl in Et2O (4 mL, 8 mmol) and stirred overnight. The supernatant was discarded. The residue washed with DCM (3×15 mL) and dried in vacuo to give 2-(piperazin-1-yl)ethyl 4-phenylpiperazine-1-carboxylate trihydrochloride (0.42 g, 98%) as a pale brown glass.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutiondissolved in EtOAc (250 mL)
  3. washwashed with 1M aq Na2CO3 solution (5×250 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by reverse phase chromatography (gradient eluting with MeOH in water, 0-100%)

Sources & evidence

ORD record
ord-589bbea86c524459ad43f9eaf6576884
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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