Benzyl Bromide → (2S)-1,4-dibenzyl-2-(4-bromophenyl)piperazine

HRID 1091377Notes

Reaction equation

HRID 1091377 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br:11][C:12]1[CH:17]=[CH:16][C:15]([C@H:18]2[CH2:23][NH:22][CH2:21][CH2:20][NH:19]2)=[CH:14][CH:13]=1>O1CCCC1>[CH2:1]([N:19]1[CH2:20][CH2:21][N:22]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:23][C@@H:18]1[C:15]1[CH:14]=[CH:13][C:12]([Br:11])=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 51894714(2S)-2-(4-Bromophenyl)piperazine

Product 1

HCID 66594629(2S)-1,4-dibenzyl-2-(4-bromophenyl)piperazineYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Hydrogen chloride in ethyl acetate solution (4N) was added to a solution of di-tert-butyl (2S)-2-(4-bromophenyl)piperazine-1,4-dicarboxylate (10 g, 22.7 mmol) in methanol (50 ml). The mixture was stirred for one hour at room temperature and the solvent was evaporated under reduced pressure to give white solid. The mixture was partitioned between saturated aqueous sodium bicarbonate and chloroform. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo to afford (2S)-2-(4-bromophenyl)piperazine as white crystals. Benzylbromide (9.7 g, 56.7 mmol) was added to a solution of sodium hydride (60% in oil, 2.0 g, 50 mmol) and (2S)-2-(4-bromophenyl)piperazine in tetrahydrofuran (50 ml) at room temperature and the mixture was stirred for one hour. 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 purified by silica gel column chromatography eluting 5-10% methanol in chloroform to furnish (2S)-1,4-Dibenzyl-2-(4-bromophenyl)piperazine (6.1 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. customThe residue was purified by silica gel column chromatography
  6. washeluting 5-10% methanol in chloroform

Sources & evidence

ORD record
ord-d63acd9afc2e4c85998f9d9abe913e3e
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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