Potassium Phosphate, Tribasic → Ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)piperidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

17.7 g of ethyl 4-allyl-1-(tert-butyloxycarbonyl)piperidine-4-carboxylate in 200 cm3 of tetrahydrofuran were cooled to a temperature in the region of −30° C. and 135 cm3 of a 0.5M solution of 9-borabicyclo-[3.3.1]nonane in tetrahydrofuran were added with stirring and under an inert atmosphere. After the addition, the temperature of the mixture was returned to about 20° C. and the mixture was stirred for 2 hours. 14.8 g of 3-fluoro-4-iodoquinoline in 430 cm3 of tetrahydrofuran, 1.3 g of palladium diphenylphosphinoferrocene chloride and 29.8 g of tribasic potassium phosphate were added. The reaction mixture was then heated at a temperature in the region of 70° C. for 20 hours. After cooling to a temperature in the region of 20° C., the reaction mass was filtered and washed with 3 times 100 cm3 of tetrahydrofuran. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue was taken up in 500 cm3 of diethyl ether, the insoluble material was washed with 3 times 100 cm3 of diethyl ether and the filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The oil obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 6 cm; height 45 cm), eluting with a dichloromethane/ethyl acetate mixture (90/10 by volume) and collecting 120-cm3 fractions. Fractions 30 to 76 were combined and then concentrated to dryness under the same conditions as above. 13.7 g of ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)-piperidine-4-carboxylate were obtained in the form of a viscous orange-colored oil.

Provenance & Evidence