Aluminium lithium hydride → (2R,5S)-1-(4-fluorobenzyl)-2,5-dimethylpiperazine

HRID 488748Notes

Reaction equation

HRID 488748 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[C@@H:12]([CH3:13])[C:11](=O)[NH:10][C@H:9]([CH3:15])[C:8]2=O)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH2:8][C@H:9]([CH3:15])[NH:10][CH2:11][C@H:12]2[CH3:13])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 69325248(3R,6S)-1-(4-Fluoro-benzyl)-3,6-dimethyl-piperazine-2,5-dione

Product 1

HCID 23405839(2R,5S)-1-(4-fluorobenzyl)-2,5-dimethylpiperazineYield 90.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3R,6S)-1-(4-fluoro-benzyl)-3,6-dimethyl-piperazine-2,5-dione (22 g, 87.9 mmol) in dry tetrahydrofuran (160 mL) at 0° C. was added a solution of lithium aluminum hydride (1M in tetrahydrofuran, 373 mL, 373 mmol) dropwise over 40 minutes. The reaction mixture was then refluxed for 4 hours, cooled to ambient temperature and slowly quenched with water. The resulting mixture was filtered through a pad of celite and the filter cake was washed with ethyl acetate. The filtrate was then concentrated, diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated in vacuo to give the title compound (17.7 g).

Workup

  1. temperatureThe reaction mixture was then refluxed for 4 hours
  2. customslowly quenched with water
  3. filtrationThe resulting mixture was filtered through a pad of celite
  4. washthe filter cake was washed with ethyl acetate
  5. concentrationThe filtrate was then concentrated
  6. additiondiluted with ethyl acetate
  7. washwashed with saturated aqueous sodium hydrogen carbonate
  8. customThe organic layer was separated
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a8ce0f64fcc1456eb2e7a3d0401b494f
Source dataset
uspto-grants-2005_12
Patent number
US06974817B2

Reaction notes

Loading…