Potassium Iodide → methyl (3R,4R)-1-[2-(3,5-difluorophenylthio)ethyl]-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

0.332 g of potassium carbonate, then 0.4 g of potassium iodide and, finally, 0.675 g of 1-[(2-bromoethyl)thio]-3,5-difluorobenzene, dissolved beforehand in 5 cm3 of acetonitrile, were added at a temperature in the region of 20° C., with stirring and under an inert atmosphere, to a solution of 0.717 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 15 cm3 of acetonitrile and 1 cm3 of methanol. The mixture was heated for 3 hours at a temperature in the region of 80° C. After cooling to a temperature in the region of 20° C., the reaction mixture was filtered and the cake was washed with 2 times 5 cm3 of acetonitrile. The filtrate was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution was carried out with a dichloromethane/methanol (95/5 by volume) mixture, and 35-cm3 fractions were collected. Fractions 18 to 21 were combined and then evaporated as above. 0.47 g of methyl (3R,4R)-1-[2-(3,5-difluorophenylthio)ethyl]-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate was obtained in the form of a viscous oil with an orange-yellow color.

Provenance & Evidence