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

Participants

Reaction Conditions

Reaction Steps

Ethyl 1-azabicyclo[2.2.1]hept-4-yl carboxylate hydrobromide salt (D13) (34 g, 0.136 mole) in concentrated hydrochloric acid (200 ml) and water (50 ml) was heated under reflux for 17 h. The solution was concentrated in vacuo to afford a white solid. Thionyl chloride (250 ml) was added and the solution heated under reflux for 3 h when a homogenous solution was obtained. The excess thionyl chloride was then removed in vacuo and the residue azeotroped with dry toluene to remove the last traces of thionyl chloride. The residue was dissolved in dry acetonitrile (250 ml) and treated with N,O-dimethyl hydroxylamine hydrochloride (16 g, 0.165 mole) and cooled to -30° C. Pyridine (53 g, 0.67 mole) was then added to the stirred reaction mixture at such a rate that the temperature did not rise above -20° C. The reaction was then allowed to warm to room temperature over 16 h. The reaction was then concentrated in vacuo to a gum and the residue partitioned between chloroform and saturated aqueous potassium carbonate solution. The organic phase was separated, dried over sodium sulphate and concentrated in vacuo to a gum. The gum was dissolved in dichloromethane and treated with decolourising charcoal filtered and reconcentrated to a gum. Recrystallisation from ether afforded 1-azabicyclo[2.2.1]hept-4-yl-N-methoxy-N-methyl carboxamide (D21) (21.2 g, 0.115 mole, 84%) as needles.

Provenance & Evidence