4-Hydroxypiperidine-1-carbonitrile → 1-(3-Isopropyl-1,2,4-oxadiazol-5-YL)piperidin-4-OL

HRID 1409738Notes

Reaction equation

HRID 1409738 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]#[N:9])[CH2:4][CH2:3]1.[OH:10][NH:11][C:12](=N)[CH:13]([CH3:15])[CH3:14]>C(OCC)(=O)C.CCOCC.[Cl-].[Cl-].[Zn+2]>[CH3:14][CH:13]([C:12]1[N:9]=[C:8]([N:5]2[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]2)[O:10][N:11]=1)[CH3:15]

Participants

6

Reactant 2

HCID 218978254-Hydroxypiperidine-1-carbonitrileHCID 178449908HCID 178449908, compound

Product 1

HCID 218977441-(3-Isopropyl-1,2,4-oxadiazol-5-YL)piperidin-4-OL

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

4-Hydroxypiperidine-1-carbonitrile (3.0 g) and N-hydroxy-2-methylpropanimidamide (2.9 g) are dissolved in ethyl acetate (20 ml) and 1 M ZnCl2 in Et2O (29 ml) is added. A precipitate forms and the solvent is decanted off. Additional Et2O (20 ml) is added to wash the precipitate and is decanted off. EtOH (20 ml) is added followed by conc. HCl (7.5 ml) and the mixture is heated to 100° C. for 3.5 h. The mixture is concentrated, redissolved in H2O (5 ml) and made basic by addition of concentrated NaHCO3. The aqueous layer is extracted with dichloromethane (2×50 mL) and the organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by silica gel chromatography (0% to 100% ethyl acetate/hexanes) to afford the title compound. LC (method 20): tR=1.56 min; Mass spectrum (APCI): m/z=212 [M+H]+.

Workup

  1. customA precipitate forms and the solvent is decanted off
  2. additionAdditional Et2O (20 ml) is added
  3. washto wash the precipitate
  4. customis decanted off
  5. additionEtOH (20 ml) is added
  6. concentrationThe mixture is concentrated
  7. dissolutionredissolved in H2O (5 ml)
  8. additionmade basic by addition of concentrated NaHCO3
  9. extractionThe aqueous layer is extracted with dichloromethane (2×50 mL)
  10. dry with materialthe organic layer is dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product is purified by silica gel chromatography (0% to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9e13efd27d1943d6b15fef0e6662df84
Source dataset
uspto-grants-2014_12
Patent number
US08921398B2

Reaction notes

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