4-Phenylpiperidine → HCID 66650798, compound

HRID 417978Notes

Reaction equation

HRID 417978 reaction equation
[C:1](=[O:22])([O:12]C1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.CCN(C(C)C)C(C)C.[C:32]1([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C=O)C>[CH:1]([OH:12])=[O:2].[C:32]1([CH:38]2[CH2:39][CH2:40][N:41]([C:1]([O:2][CH2:3][CH2:4][N:5]3[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]3)=[O:22])[CH2:42][CH2:43]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 698734-PhenylpiperidineHCID 81531DiisopropylethylamineHCID 574450072-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate2×

Product 1

HCID 66650798HCID 66650798, compoundYield 79.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 680 mg, 2.2 mmol) was dissolved in DMF (20 mL). DIPEA (0.52 mL, 3.0 mmol) and 4-phenylpiperidine (322 mg, 2.0 mmol) were added and the reaction mixture was stirred at room temperature for 65 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (40 mL) and washed with 1 M aq Na2CO3 solution (6×50 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by reverse phase column chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%) to give 2-(4-methylpiperazin-1-yl)ethyl 4-phenylpiperidine-1-carboxylate formate (330 mg, 42%) as a yellow oil.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (40 mL)
  3. washwashed with 1 M aq Na2CO3 solution (6×50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by reverse phase column chromatography (gradient
  7. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)

Sources & evidence

ORD record
ord-c1bdf5e223ee474ab73160f9d6503301
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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