Diisopropylethylamine → [1-(2-Methoxyethyl)piperidin-4-yl]methyl 4-(4-chlorophenyl)piperazine-1-carboxylate dihydrochloride

HRID 417960Notes

Reaction equation

HRID 417960 reaction equation
[C:1](=[O:24])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][O:12][CH3:13])[CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.[ClH:34].Cl.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)=[CH:39][CH:38]=1>CN(C=O)C>[ClH:36].[ClH:34].[Cl:36][C:37]1[CH:38]=[CH:39][C:40]([N:43]2[CH2:48][CH2:47][N:46]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][N:7]([CH2:10][CH2:11][O:12][CH3:13])[CH2:8][CH2:9]3)=[O:24])[CH2:45][CH2:44]2)=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12212341Piperazine, 1-(4-chlorophenyl)-, hydrochloride (1:2)HCID 57955470(1-(2-Methoxyethyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate2×

Product 1

HCID 66650941[1-(2-Methoxyethyl)piperidin-4-yl]methyl 4-(4-chlorophenyl)piperazine-1-carboxylate dihydrochlorideYield 66.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1-(2-methoxyethyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 3; 1.01 g, 3.0 mmol) was dissolved in DMF (10 mL). DIPEA (1.74 mL, 5.0 mmol) and, 4-(4-chlorophenyl)piperazine dihydrochloride (808 mg, 3.0 mmol) were added and the reaction mixture was stirred at room temperature for 14 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 (5×30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 96:4 mixture of DCM:MeOH) followed by reverse phase column chromatography (gradient eluting with MeOH in water, 0-100%). The residue was dissolved in DCM (10 mL) and 2M HCl in Et2O (3 mL) was added. The reaction mixture was then concentrated in vacuo to give [1-(2-methoxyethyl)piperidin-4-yl]methyl 4-(4-chlorophenyl)piperazine-1-carboxylate dihydrochloride (468 mg, 39.5%) as white solid.

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 (5×30 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 96:4 mixture of DCM
  9. washMeOH) followed by reverse phase column chromatography (gradient eluting with MeOH in water, 0-100%)
  10. dissolutionThe residue was dissolved in DCM (10 mL)
  11. addition2M HCl in Et2O (3 mL) was added
  12. concentrationThe reaction mixture was then concentrated in vacuo

Sources & evidence

ORD record
ord-48cf2b5269e447e394d5ae8ad0760c6a
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

Loading…