Hydrochloric Acid → N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride

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Reaction Steps

10.5 g (0.063 mole) of methyl 3-methoxypicolinate and 17.6 g (0.137 mole) of 1-ethyl-2-(aminomethyl)-pyrrolidine are heated under nitrogen for 6 hours to 80° C. The excess base is distilled off in a high vacuum at 50° C and the oily residue is dissolved in methylene chloride and treated with 12 ml of 6 N ethanolic hydrochloric acid. The solvent is evaporated in vacuo and the oily residue is crystallised by trituration with ether. The crystals are collected by filtration and recrystallised from isopropanol-ethyl acetate to yield crude N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride. The combined mother solutions are concentrated in vacuo and the free base is recovered as solution with 2 N sodium hydroxide solution and methylene chloride. The solution is concentrated, the residue dissolved in chloroform and chromatographed through a column of 60 g of silica gel with chloroform-methanol (98:2) as eluant. The base so obtained is again converted with ethanolic hydrochloric acid into the hydrochloride, which is recrystallised from ether. The combined crude hydrochlorides are recrystallised from isopropanol-ethyl acetate and yield pure N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride with a melting point of 162°-163° C.

Provenance & Evidence