1-Phenylpiperazine → (Piperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate

HRID 417958Notes

Reaction equation

HRID 417958 reaction equation
[C:1](=[O:27])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH:3](C(OC(C)(C)C)=O)[CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.[C:37]1([N:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C=O)C>[C:37]1([N:43]2[CH2:48][CH2:47][N:46]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][NH:7][CH2:8][CH2:9]3)=[O:27])[CH2:45][CH2:44]2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 70961-PhenylpiperazineHCID 81531DiisopropylethylamineHCID 66650794(tert-Butoxycarbonyl)piperidin-4-ylmethyl 4-nitrophenyl carbonate2×

Product 1

HCID 66650828(Piperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylateYield 96.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 2; 5.0 g, 13.1 mmol) was dissolved in DMF (30 mL). DIPEA (4.58 mL, 26.3 mmol) and 1-phenylpiperazine (2.01 mL, 13.1 mmol) were added. The reaction mixture was stirred at room temperature for 18 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and then washed sequentially with sat aq NaHCO3 solution (6×200 mL), 10% citric acid solution (50 mL) and brine (50 mL). The solution was dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (20 mL) and TFA (10 mL) was added. The reaction mixture was stirred at room temperature for 3 hours and then concentrated in vacuo. The residue was dissolved in water (20 mL), sat aq NaHCO3 solution (100 mL) was added and the aqueous layer was extracted with DCM (3×200 mL). The combined organic layers were then washed with brine (50 mL), dried (MgSO4) and the solution was concentrated in vacuo to give (piperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate (3.825 g, 95.9% yield) as a yellow solid.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (300 mL)
  3. washwashed sequentially with sat aq NaHCO3 solution (6×200 mL), 10% citric acid solution (50 mL) and brine (50 mL)
  4. dry with materialThe solution was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DCM (20 mL)
  7. additionTFA (10 mL) was added
  8. stirringThe reaction mixture was stirred at room temperature for 3 hours
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in water (20 mL)
  11. additionwas added
  12. extractionthe aqueous layer was extracted with DCM (3×200 mL)
  13. washThe combined organic layers were then washed with brine (50 mL)
  14. dry with materialdried (MgSO4)
  15. concentrationthe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-5489dd064bd94fb6a0f9423e4cbc711d
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

Loading…