Water → (3R,4R)-methyl 4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)-1-(3-(2,3,5-trifluorophenyl)prop-2-ynyl)piperidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 17.28 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)-piperidine-3-carboxylate in 173 cm3 of triethylamine is stirred for 5 minutes under an inert atmosphere at a temperature in the region of 20° C. 4.05 g of tetrakis(triphenylphosphine)palladium, 0.834 g of cuprous iodide and 7.9 g of 1-bromo-2,3,5-trifluorobenzene are added. The mixture is stirred for 2 hours at a temperature in the region of 80° C. After cooling to approximately 20° C., 150 cm3 of ethyl acetate and 150 cm3 of water are added to the reaction mixture, which is then separated after settling out. The aqueous phase is extracted with 3 times 150 cm3 of ethyl acetate. The organic phases are pooled, washed with 5 times 150 cm3 of water, dried over sodium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20–45μ; diameter 7 cm; 600 g), eluting with pure ethyl acetate and collecting first a fraction of 2.5 1, and then fractions of 250 cm3. Fractions 2 to 29 are pooled and then concentrated as above. 18.4 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-piperidine-3-carboxylate, in the form of a yellow oil, are obtained.

Provenance & Evidence