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

Participants

Reaction Steps

0.263 g of triphenylphosphine and then 0.85 g of tetrakis(triphenylphosphine)palladium, 0.4 g of cuprous iodide, and 1.75 cm3 of 2-iodothiophene were added with stirring, at a temperature in the region of 20° C. and under an inert atmosphere, to a solution of 4.3 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[prop-2-ynyl]piperidine-3-acetate in 100 cm3 of acetonitrile. The mixture was stirred for 10 minutes and then 2.95 cm3 of triethylamine were added. After stirring for 48 hours at a temperature in the region of 20° C., the mixture was filtered through celite and the insoluble material was washed with 2 times 50 cm3 of acetonitrile. The filtrate was 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 4.5 cm; silica volume 500 cm3), elution was carried out with pure ethyl acetate, and approximately 60-cm3 fractions were collected. The fractions corresponding to the expected product were combined. These fractions were concentrated under the above conditions. 4 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]piperidine-3-acetate were obtained in the form of an oil with a yellow color.

Provenance & Evidence