Hydroxyamine hydrochloride → 4-((2S)-1,4-dibenzylpiperazin-2-yl)benzonitrile

HRID 1091379Notes

Reaction equation

HRID 1091379 reaction equation
Cl.[NH2:2]O.[CH2:4]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][C@@H:12]1[C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>[OH-].[Na+].C(O)C>[CH2:4]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][C@@H:12]1[C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:2])=[CH:26][CH:25]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 866345574-((2S)-1,4-dibenzylpiperazin-2-yl)benzaldehyde

Product 1

HCID 665948754-((2S)-1,4-dibenzylpiperazin-2-yl)benzonitrileYield 64.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

Hydroxylamine hydrochloride (0.5 g, 7.75 mmol) was added to a solution of 4-((2S)-1,4-dibenzylpiperazin-2-yl)benzaldehyde (2.2 g, 5.94 mmol) in 1N aqueous sodium hydroxide (10 ml) and ethanol (10 ml) at room temperature and stirred for 2 hours. The mixture was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was dissolved in acetic acid (10 ml) and was stirred at 80° C. for 6 hours. The solvent was removed under reduced pressure and the residue was partitioned between saturated aqueous sodium bicarbonate and chloroform. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 5-10% methanol in chloroform to furnish 4-((2S)-1,4-dibenzylpiperazin-2-yl)benzonitrile (1.4 g, 64%) as a colorless oil.

Workup

  1. customThe mixture was partitioned between water and chloroform
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in acetic acid (10 ml)
  6. stirringwas stirred at 80° C. for 6 hours
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was partitioned between saturated aqueous sodium bicarbonate and chloroform
  9. washThe organic layer was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel column chromatography
  13. washeluting 5-10% methanol in chloroform

Sources & evidence

ORD record
ord-7120c25caed940808c8b6940844c9789
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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