2-(3-Hydroxypiperidin-1-YL)acetonitrile → 1-(2-Aminoethyl)piperidin-3-ol

HRID 226247Notes

Reaction equation

HRID 226247 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH:7][CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([CH2:14][C:15]#[N:16])[CH2:9]1>C1COCC1>[NH2:16][CH2:15][CH2:14][N:10]1[CH2:11][CH2:12][CH2:13][CH:8]([OH:7])[CH2:9]1

Participants

4

Reactant 2

HCID 116939192-(3-Hydroxypiperidin-1-YL)acetonitrileHCID 21226445Aluminium lithium hydride

Product 1

HCID 47124711-(2-Aminoethyl)piperidin-3-olYield 63.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LiAlH4 (2.44 g, 64.2 mmol) was added to dry THF (20 mL) at 0° C. in a three-neck round bottom flask under N2. The solution was stirred for 15 min. before the 3-hydroxypiperidin-1-yl-acetonitrile (3 g, 21.4 mmol), diluted in dry THF (5 mL), was added slowly via syringe. The reaction mixture was then refluxed 5 h before allowing the solution to cool to RT. Excess of LiAlH4 was destroyed by dropwise addition of 2.4 mL of H2O, 2.4 mL of NaOH (15%) and finally EtOAc was added dropwise until no effervesence was observed. The formed granular precipitate (lithium hydroxide and aluminium hydroxide) was filtered off and washed several times with CH2Cl2 and EtOAc. The organic layer was dried (MgSO4) and the solvent was removed in vacuo to yield a thick yellowish oil. The title-compound was purified by kugelrohr distillation (172° C., 0.05 mbar) and obtained as a straw coloured oil (1.95 g, 63%). δH (250 MHz;

Workup

  1. additionwas added slowly via syringe
  2. temperatureThe reaction mixture was then refluxed 5 h
  3. customExcess of LiAlH4 was destroyed by dropwise addition of 2.4 mL of H2O, 2.4 mL of NaOH (15%) and finally EtOAc
  4. additionwas added dropwise until no effervesence
  5. filtrationThe formed granular precipitate (lithium hydroxide and aluminium hydroxide) was filtered off
  6. washwashed several times with CH2Cl2 and EtOAc
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customthe solvent was removed in vacuo
  9. customto yield a thick yellowish oil
  10. distillationThe title-compound was purified by kugelrohr distillation (172° C., 0.05 mbar)

Sources & evidence

ORD record
ord-c9aced554aa44c8aac75fe58a20c7810
Source dataset
uspto-grants-2009_07
Patent number
US07557215B2

Reaction notes

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