Sodium Hydroxide → (3S)-1-Benzyl-3-(propan-2-yl)piperazine

HRID 1063853Notes

Reaction equation

HRID 1063853 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[CH2:19][C:18](=O)[NH:17][C@@H:16]([CH:21]([CH3:23])[CH3:22])[C:15]1=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[OH-].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>ClCCl.O.O1CCCC1>[CH2:7]([N:14]1[CH2:19][CH2:18][NH:17][C@@H:16]([CH:21]([CH3:23])[CH3:22])[CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24436Sodium SulfateHCID 21226445Aluminium lithium hydrideHCID 23402343HCID 23402343, compound

Product 1

HCID 17750438(3S)-1-Benzyl-3-(propan-2-yl)piperazineYield 42.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To 100 mL tetrahydrofuran cooled to 0° C. were added 9 mL (8.9 mMol) lithium aluminum hydride (1.0 M in tetrahydrofuran) dropwise. To this was added dropwise a solution of 1.0 gm (4.06 mmol) 1-benzyl-2,5-dioxo-3(S)-isopropylpiperazine in 50 mL dichloromethane over 30 minutes. The reaction mixture was then heated at reflux over night. The reaction mixture was then cooled to 0° C. and was stirred vigorously while being treated sequentially with 1 mL water, 1 mL 5N sodium hydroxide, 2 mL water, and 5 gm sodium sulfate. After stirring for 30 minutes the reaction mixture was filtered and the filter cake washed with dichloromethane. The filtrate was concentrated under reduced pressure and the yellow waxy solid residue was subjected to silica gel chromatography, eluting with dichloromethane containing 0–3% methanol. Fractions containing product were combined and concentrated under reduced pressure to provide 0.38 gm (42%) of the title compound.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux over night
  3. stirringAfter stirring for 30 minutes the reaction mixture
  4. filtrationwas filtered
  5. washthe filter cake washed with dichloromethane
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. washeluting with dichloromethane containing 0–3% methanol
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-902f58f456b74c57a76b5b78ddbce1b0
Source dataset
uspto-grants-2005_11
Patent number
US06967201B1

Reaction notes

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