Sodium hydride → 2-[3-Methyl-1,2,4-oxadiazol-5-yl]-8-methyl-8-azabicyclo[3.2.1]oct-2-ene

HRID 1597718Notes

Reaction equation

HRID 1597718 reaction equation
[C:1](=[N:4][OH:5])([NH2:3])[CH3:2].[H-].[Na+].[CH3:8][N:9]1[C@H:13]2[C:14]([C:17](OC)=O)=[CH:15][CH2:16][C@@H:10]1[CH2:11][CH2:12]2>C1COCC1>[CH3:2][C:1]1[N:3]=[C:17]([C:14]2[CH:13]3[N:9]([CH3:8])[CH:10]([CH2:16][CH:15]=2)[CH2:11][CH2:12]3)[O:5][N:4]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 30926N-HydroxyacetamidineHCID 119478(-)-Anhydroecgonine methyl ester

Product 1

HCID 189853812-[3-Methyl-1,2,4-oxadiazol-5-yl]-8-methyl-8-azabicyclo[3.2.1]oct-2-ene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acetamide oxime (500 mg, 6.75 mol) suspended in THF (50 mL) under nitrogen was heated at 60° C. with NaH (132 mg, 5.5 mmol in oil dispersion) for 1 h. Anhydroecgonine methyl ester (2.76 ml) and 4 A° molecular sieves (2 g) were added and the reaction mixture heated under reflux for 3 h. After cooling, the reaction mixture was filtered and the solvent removed in vacuo. The residue was chromatographed on a silica gel column eluting with CHCl3 --CH3OH (95:5) to give the free base.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureunder reflux for 3 h
  3. temperatureAfter cooling
  4. filtrationthe reaction mixture was filtered
  5. customthe solvent removed in vacuo
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with CHCl3 --CH3OH (95:5)
  8. customto give the free base

Sources & evidence

ORD record
ord-7732e2063a78441189b8f0aa5ea82fc8
Source dataset
uspto-grants-1998_04
Patent number
US05736123

Reaction notes

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