Aluminium lithium hydride → (2R)-2-(4-methoxybenzyl)-4-benzylpiperazine

HRID 1375042Notes

Reaction equation

HRID 1375042 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[CH2:19][C:18](=O)[NH:17][C@H:16]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:15]1=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>O1CCCC1>[CH3:29][O:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][C@@H:16]2[CH2:15][N:14]([CH2:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:19][CH2:18][NH:17]2)=[CH:27][CH:26]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 54330683(3R)-1-benzyl-3-(4-methoxybenzyl)piperazine-2,5-dione

Product 1

HCID 53781111(2R)-2-(4-methoxybenzyl)-4-benzylpiperazineYield 105.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen atmosphere, to a suspension of lithium aluminum hydride (0.85 g) in tetrahydrofuran (65 ml) was added (3R)-1-benzyl-3-(4-methoxybenzyl)piperazine-2,5-dione (3.65 g) portionwise under ice-bath cooling. The reaction mixture was refluxed with stirring for one hour. After cooling, it was quenched by sequential addition of water (0.85 ml), 15% aqueous sodium hydroxide (0.85 ml), and water (2.5 ml) and the whole was stirred at room temperature for 30 minutes. The resulting insoluble material was removed by filtration, and the filtrate was added to a mixture of ethyl acetate (50 ml) and brine (70 ml). The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure to give (2R)-2-(4-methoxybenzyl)-4-benzylpiperazine (3.51 g) as a syrup.

Workup

  1. temperaturecooling
  2. temperatureThe reaction mixture was refluxed
  3. temperatureAfter cooling
  4. customit was quenched by sequential addition of water (0.85 ml), 15% aqueous sodium hydroxide (0.85 ml), and water (2.5 ml)
  5. stirringthe whole was stirred at room temperature for 30 minutes
  6. customThe resulting insoluble material was removed by filtration
  7. additionthe filtrate was added to a mixture of ethyl acetate (50 ml) and brine (70 ml)
  8. customThe organic layer was separated
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b7c2b764800b413daae36ca3c4a52c9a
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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