Sodium Hydroxide → 4-[3-(3-Fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 0.8 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluoro-phenoxy)ethyl]piperidine-4-carboxylate in 50 cm3 of dioxane, 50 cm3 of methanol and 4.4 cm3 of aqueous 5N sodium hydroxide solution was stirred at a temperature in the region of 70° C. for 18 hours. A further 4.4 cm3 of aqueous 5N sodium hydroxide solution were added to the reaction mixture, which was stirred for 6 hours in the region of 70° C. After cooling to about 20° C., the reaction mass was concentrated to dryness under reduced pressure (1.1 kPa) at a temperature in the region of 5° C. The residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 4 cm; height 20 cm), eluting with a mixture of chloroform/methanol/aqueous ammonia (12/3/0.5 by volume) and collecting 60-cm3 fractions. Fractions 8 to 19 were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. and oven-dried under reduced pressure (10 kPa) at about 50° C. 0.59 g of 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylic acid was obtained in the form of a white solid melting at about 120° C.

Provenance & Evidence