Diisopropylethylamine → (1-Piperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate

HRID 417951Notes

Reaction equation

HRID 417951 reaction equation
[C:1](=[O:27])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.Cl.Cl.[Cl:39][C:40]1[CH:45]=[CH:44][C:43]([N:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)=[CH:42][CH:41]=1>CN(C=O)C>[Cl:39][C:40]1[CH:41]=[CH:42][C:43]([N:46]2[CH2:51][CH2:50][N:49]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][NH:7][CH2:8][CH2:9]3)=[O:27])[CH2:48][CH2:47]2)=[CH:44][CH:45]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12212341Piperazine, 1-(4-chlorophenyl)-, hydrochloride (1:2)HCID 57955467tert-Butyl 4-((((4-nitrophenoxy)carbonyl)oxy)methyl)piperidine-1-carboxylate2×

Product 1

HCID 66651134(1-Piperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylateYield 45.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 2; 10.0 g, 26.3 mmol), was dissolved in DMF (50 mL). DIPEA (16.0 mL, 92.0 mmol) and 4-(4-chlorophenyl)piperazine dihydrochloride (7.09 g, 26.3 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 (300 mL) and washed with a 1 M aq Na2CO3 solution (6×200 mL), 10% citric acid solution (50 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in a mixture of DCM (100 mL) and TFA (20 mL), stirred for 4 hours and then concentrated in vacuo. The residue was dissolved in 1 M aq Na2CO3 solution (220 mL), and extracted with DCM (3×200 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was recrystallised from EtOAc to give (1-piperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate (4.07 g, 45.7%) as a cream solid.

Workup

  1. concentrationthe reaction mixture was then concentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in EtOAc (300 mL)
  3. washwashed with a 1 M aq Na2CO3 solution (6×200 mL), 10% citric acid solution (50 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in a mixture of DCM (100 mL) and TFA (20 mL)
  7. stirringstirred for 4 hours
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in 1 M aq Na2CO3 solution (220 mL)
  10. extractionextracted with DCM (3×200 mL)
  11. washThe combined organic layers were washed with brine (50 mL)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. customThe residue was recrystallised from EtOAc

Sources & evidence

ORD record
ord-8b459550ae3945b8b18fc152a46a0f6d
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

Loading…