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

Participants

Reaction Conditions

Reaction Steps

4.8 cm3 of triethylamine were added with stirring, at a temperature in the region of 20° C. and under an inert atmosphere, to a solution of 5 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate in 60 cm3 of dimethylformamide. After stirring for 15 minutes at this temperature, 1.5 cm3 of propargyl bromide were added over approximately 15 minutes and then, after 15 minutes, the mixture was heated at a temperature in the region of 45° C. for 4 hours. After cooling to approximately 20° C., the reaction mixture was poured onto approximately 700 cm3 of water and then the mixture was extracted with 4 times 80 cm3 of diethyl ether. The combined extracts were washed with 3 times 80 cm3 of water, dried, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 4 cm; silica volume 500 cm3), elution was carried out with pure ethyl acetate, and 60-cm3 fractions were collected. Fractions 9 to 20 were combined and then concentrated as under the above conditions. 4.3 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[prop-2-ynyl]piperidine-3-acetate were obtained in the form of an oil with a yellow color.

Provenance & Evidence