Water → methyl (3R,4R)-1-(3-prop-2-ynyl)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

23.7 cm3 of triethylamine and 6.35 cm3 of propargyl bromide are added at a temperature in the region of 20° C., with stirring and under an inert atmosphere, to a solution of 14.43 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 350 cm3 of anhydrous dimethylformamide. After heating for 5 hours at a temperature in the region of 45° C., the reaction mixture is cooled to approximately 20° C., poured into 190 cm3 of water and 190 cm3 of ethyl acetate, and then extracted with 3 times 250 cm3 of ethyl acetate. The organic extracts are combined, washed 3 times with 250 cm3 of water, dried over sodium sulfate, filtered and concentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C. The residue is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 8 cm; mass 600 g), elution being carried out with ethyl acetate and an ethyl acetate/methanol (95/05 by volume) mixture and 400-cm3 fractions being collected. Fractions 3 to 13 are combined and then concentrated under the above conditions. 17.5 g of methyl (3R,4R)-1-(3-prop-2-ynyl)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate are obtained.

Provenance & Evidence