Ethanol → 2-(1-Pyrrolidinylmethyl)-1-azabicyclo[2.2.2]octan-3-one oxime

HRID 327384Notes

Reaction equation

HRID 327384 reaction equation
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=O)[CH2:3]2.[OH-:11].[Na+].[NH:13]1[CH2:17]C[CH2:15][CH2:14]1.C=O.S([O-])([O-])(=O)=O.[Mg+2].Cl.[NH2:27]O.C[O-].[Na+].[CH2:32](O)[CH3:33]>CCOCC>[N:13]1([CH2:17][CH:3]2[C:4](=[N:27][OH:11])[CH:5]3[CH2:8][CH2:9][N:2]2[CH2:7][CH2:6]3)[CH2:33][CH2:32][CH2:15][CH2:14]1

Participants

10

Reactant 8

HCID 702Ethanol2×HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 31268PyrrolidineHCID 1020191-Azabicyclo(2.2.2)octan-3-one, hydrochloride (1:1)HCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium Methoxide2×

Product 1

HCID 740017462-(1-Pyrrolidinylmethyl)-1-azabicyclo[2.2.2]octan-3-one oximeYield 36%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A suspension of quinuclidine-3-one hydrochloride (16.2 g, 0.1 mole) in 95% ethanol (25 ml) was treated with 50% sodium hydroxide (8.0 g, 0.1 mole) and stirred until homogeneous. In a separate reactor a cooled (0° C.) solution of pyrrolidine (10.7 g, 0.15 mole) in 95% ethanol (25 ml) was treated dropwise with 37% aqueous formaldehyde (11.5 ml, 0.15 mole), and the solution was stirred at 25° C. for 30 minutes. The two solutions were combined and the mixture was refluxed for 4 hours, cooled, and added to ether (250 ml). Magnesium sulfate was added, and the mixture was stirred for 15 minutes and filtered. The filtrate was concentrated in vacuo, dissolved in methanol (100 ml), and treated with hydroxylamine hydrochloride (7.65 g, 110 mmoles), then with 25% sodium methoxide (2.2 g, 10 mmoles). After 2 hours at room temperature additional 25% sodium methoxide (21.6 g, 100 mmoles) was added and after 15 minutes the solution was filtered. The filtrate was concentrated in vacuo to a residue, which was dissolved in methylene chloride (150 ml) and filtered. The filtrate was concentrated in vacuo, and the residue was triturated from cold ether, then from cold acetonitrile ether to afford 8.09 g (36%) of fine colorless needles, mp 194°-195° C.

Workup

  1. stirringthe solution was stirred at 25° C. for 30 minutes
  2. temperaturethe mixture was refluxed for 4 hours
  3. temperaturecooled
  4. stirringthe mixture was stirred for 15 minutes
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. dissolutiondissolved in methanol (100 ml)
  8. filtrationwas filtered
  9. concentrationThe filtrate was concentrated in vacuo to a residue, which
  10. dissolutionwas dissolved in methylene chloride (150 ml)
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated in vacuo
  13. customthe residue was triturated from cold ether

Sources & evidence

ORD record
ord-57428ed6789042f7bf5efcc0077c655a
Source dataset
uspto-grants-1993_12
Patent number
US05273972

Reaction notes

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