1-Phenylpiperazine → (1-Methylpiperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate formate

HRID 417950

Reaction equation

HRID 417950 reaction equation
[C:1](=[O:21])([O:11]C1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.[C:31]1([N:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C=O)C>[CH:1]([OH:11])=[O:2].[C:31]1([N:37]2[CH2:42][CH2:41][N:40]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][N:7]([CH3:10])[CH2:8][CH2:9]3)=[O:21])[CH2:39][CH2:38]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 70961-PhenylpiperazineHCID 81531DiisopropylethylamineHCID 57445006(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate2×

Product 1

HCID 66650713(1-Methylpiperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate formateYield 17.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 1; 5.70 g, 19.4 mmol) was dissolved in DMF (40 mL). DIPEA (6.75 mL, 38.7 mmol) and 1-phenyl-piperazine (2.96 mL, 19.4 mmol) were added. The reaction mixture was stirred at room temperature for 6 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and washed sequentially with sat aq NaHCO3 solution (6×200 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 98:1:1 mixture of DCM:MeOH:DIPEA) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-80%) to give (1-methylpiperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate formate (0.63 g, 10.3%) as a viscous yellow oil.

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), brine (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 98:1:1 mixture of DCM
  9. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-80%)

Sources & evidence

ORD record
ord-874c56c1b5c545219f596cc56926c21b
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Linked notes

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