Triethylamine → 1-Azabicyclo[2.2.1]hept-4-yl-N-methoxy-N-methyl carboxamide

HRID 374256Notes

Reaction equation

HRID 374256 reaction equation
[N:1]12[CH2:7][C:4]([C:8]([O:10]CC)=O)([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.Cl.[CH3:14][NH:15][O:16][CH3:17].C(N(CC)CC)C>Cl.S(Cl)(Cl)=O>[N:1]12[CH2:7][C:4]([C:8]([N:15]([O:16][CH3:17])[CH3:14])=[O:10])([CH2:3][CH2:2]1)[CH2:5][CH2:6]2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 15663604Ethyl 1-azabicyclo[2.2.1]heptane-4-carboxylate

Product 1

HCID 156636181-Azabicyclo[2.2.1]hept-4-yl-N-methoxy-N-methyl carboxamide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 24386Thionyl ChlorideSolvent

Procedure

Ethyl 1-azabicyclo[2.2.1]hept-4-ylcarboxylate (D16, 1.75g, 0.01 mole) in concentrated hydrochloric acid (50ml) was heated under reflux for 1.5h. The reaction was then concentrated in vacuo to give a solid which was dissolved in thionyl chloride (30 ml) and heated under reflux for 1.5 h. The mixture was then evaporated to dryness, and freed from residual thionyl chloride by co-evaporation which toluene. The residue was then dissolved in dry acetonitrile (50 ml) and treated with N,O-dimethylhydroxylamine hydrochloride (0.73g, 0.0075 mole) and triethylamine (4.5ml, 0.032 mole). The mixture was stirred overnight at room temperature and then filtered to remove most of the triethylamine hydrochloride. The filtrate was evaporated to dryness and saturated potassium carbonate solution was added. The product was then extracted into chloroform (3×100ml) and the combined extracts were dried (Na2SO4), filtered and evaporated to dryness to give the title compound (D17) as a white solid (0.79g, 41%).

Workup

  1. temperatureunder reflux for 1.5h
  2. concentrationThe reaction was then concentrated in vacuo
  3. customto give a solid which
  4. temperatureheated
  5. temperatureunder reflux for 1.5 h
  6. customThe mixture was then evaporated to dryness
  7. dissolutionThe residue was then dissolved in dry acetonitrile (50 ml)
  8. filtrationfiltered
  9. customto remove most of the triethylamine hydrochloride
  10. customThe filtrate was evaporated to dryness and saturated potassium carbonate solution
  11. additionwas added
  12. extractionThe product was then extracted into chloroform (3×100ml)
  13. dry with materialthe combined extracts were dried (Na2SO4)
  14. filtrationfiltered
  15. customevaporated to dryness

Sources & evidence

ORD record
ord-109cb3388eb14d9f9b6a04db14eb33ca
Source dataset
uspto-grants-1992_11
Patent number
US05166357

Reaction notes

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