Formaldehyde → 4-(5-Methoxy-3-pyridinyl)-6-methyl-6-azabicyclo[3.2.1]oct-3-ene

HRID 749133Notes

Reaction equation

HRID 749133 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:15]3[CH2:16][CH:12]([CH2:13][NH:14]3)[CH2:11][CH:10]=2)[CH:6]=[N:7][CH:8]=1.[CH2:17]=O>C(O)=O>[CH3:17][N:14]1[CH2:13][CH:12]2[CH2:16][CH:15]1[C:9]([C:5]1[CH:6]=[N:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)=[CH:10][CH2:11]2

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 57485788HCID 57485788, compound

Product 1

HCID 574863494-(5-Methoxy-3-pyridinyl)-6-methyl-6-azabicyclo[3.2.1]oct-3-eneYield 56%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A mixture of 4-(5-methoxy-3-pyridinyl)-6-azabicyclo[3.2.1]oct-3-ene (15 mg, 0.07 mmol), aqueous formaldehyde (37%, 0.25 mL) and 90% formic acid (1 mL) was heated at reflux for 1½ h. The mixture was concentrated under reduced pressure, and the remaining volatiles were removed by azeotropic evaporation with methanol (thee times). The residue was made basic with dilute aqueous sodium hydroxide and extracted into dichloromethane. The extracts were dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was chromatographed on a silica gel column, eluting with 90:10:1 dichloromethane/methanol/concentrated ammonium hydroxide. Concentration of selected fractions gave the product as an oil (9.0 mg, 56%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1½ h
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customthe remaining volatiles were removed by azeotropic evaporation with methanol (thee times)
  5. extractionextracted into dichloromethane
  6. dry with materialThe extracts were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was chromatographed on a silica gel column
  10. washeluting with 90:10:1 dichloromethane/methanol/concentrated ammonium hydroxide

Sources & evidence

ORD record
ord-e8fcf378bbcc404b807d5d84014d9274
Source dataset
uspto-grants-2008_07
Patent number
US07402592B2

Reaction notes

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