Aluminium lithium hydride → (3S)-1-Benzyl-3-(propan-2-yl)piperazine

HRID 419671Notes

Reaction equation

HRID 419671 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][CH:8]([C@H:10]1[CH2:15][N:14]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:13](=O)[C:12](=O)[NH:11]1)[CH3:9]>C1COCC1>[CH3:9][CH:8]([C@@H:10]1[NH:11][CH2:12][CH2:13][N:14]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:15]1)[CH3:7]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 59452588(5S)-5-(1-methylethyl)-1-(phenylmethyl)-2,3-piperazinedione

Product 1

HCID 17750438(3S)-1-Benzyl-3-(propan-2-yl)piperazineYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

LAH (1.87 g, 49.3 mmol) was suspended in 60 mL of THF with stirring and cooled to 0° C. under an inert atmosphere. (5S)-5-(1-methylethyl)-1-(phenylmethyl)-2,3-piperazinedione (2.43 g, 9.87 mmol) was dissolved in 50 mL of THF and added dropwise via addition funnel over 20 min. The funnel was rinsed with an additional 10 mL of THF. The reaction was warmed to rt and stirred for 2 days. The reaction was quenched by the careful sequential addition of 1.9 mL of H2O, 1.9 mL of 1N NaOH (aq.), and 5.7 mL of H2O. The slurry was stirred for 30 min and filtered. The solids were washed with DCM. The filtrate was concentrated in vacuo. Purification by flash chromatography afforded the title compound of step B (1.68 g, 7.69 mmol, 78%). 1H NMR (400 MHz, DMSO-d6) δ 7.33-7.18 (m, 5H), 3.40 (AB, ΔνAB=34.5 Hz, JAB=13.2 Hz, 2H), 2.78 (m, 1H), 2.71-2.51 (m, 3H), 2.28 (m, 1H), 1.88-1.72 (m, 2H), 1.63 (t, J=10.3 Hz, 1H), 1.45 (m, 1H), 0.83 (d, J=6.8 Hz, 3H), 0.79 (d, J=6.8 Hz, 3H).

Workup

  1. additionadded dropwise via addition funnel over 20 min
  2. washThe funnel was rinsed with an additional 10 mL of THF
  3. temperatureThe reaction was warmed to rt
  4. stirringstirred for 2 days
  5. customThe reaction was quenched by the careful sequential addition of 1.9 mL of H2O, 1.9 mL of 1N NaOH (aq.), and 5.7 mL of H2O
  6. stirringThe slurry was stirred for 30 min
  7. filtrationfiltered
  8. washThe solids were washed with DCM
  9. concentrationThe filtrate was concentrated in vacuo
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-30d571a0f2c84424a71e489fd7cd97f6
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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