Potassium Iodide → Methyl (3rs,4rs)-4-[3-(r,s)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-acetate

Participants

Reaction Conditions

Reaction Steps

A mixture of 6.5 g of methyl (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-piperidine-3-acetate dihydrochloride, 3.9 g of 2-(2-bromoethylsulfanyl)-1,4-difluorobenzene dissolved in 10 cm3 of dimethylformamide, 2.32 g of potassium iodide, 5.8 g of potassium carbonate and 3.93 cm3 of triethylamine in 200 cm3 of acetonitrile is heated with stirring and under an inert atmosphere for 22 hours at a temperature in the region of 70° C. After cooling to a temperature in the region of 20° C., the reaction medium is filtered and the insoluble material is washed with 2 times 30 cm3 of acetonitrile. The filtrate is evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue is taken up with 100 cm3 of distilled water and 150 cm3 of ethyl acetate. The organic phase is washed with 3 times 100 cm3 of distilled water and 2 times 100 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and evaporated according to the conditions described above. The oil obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40–60 μm; diameter 4 cm), eluting with a mixture of cyclohexane-ethyl acetate (50/50 by volume) and collecting fractions of 60 cm3. The fractions containing the expected product are pooled and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 1.7 g of methyl (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-acetate, in the form of an orange-colored viscous oil, are obtained.

Provenance & Evidence