Potassium Phosphate, Tribasic → methyl (3RS,4RS)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-propyl]-1-(tert-butyloxycarbonyl)piperidine-3-carboxylate

Participants

Reaction Steps

A solution of 1.45 g of methyl (3RS,4RS)-1-(tert-butyloxycarbonyl)-4-allylpiperidine-3-carboxylate in 20-cm3 of tetrahydrofuran was slowly added, at a temperature in the region of 0° C. with stirring and under an inert atmosphere, to 16-cm3 of a 0.5 M solution of 9-borabicyclo[3.3.1]nonane in tetrahydrofuran. The mixture was then brought to a temperature in the region of 20° C. while the stirring was continued for a further 4 hours. 1.52 g of 4-iodo-3-fluoro-6-methoxyquinoline in solution in 40-cm3 of tetrahydrofuran were added, followed by 100 mg of palladiumdiphenylphosphinoferrocene chloride and finally 3.18 g of tribasic potassium phosphate. The reaction mixture was heated for 15 hours under reflux and then filtered in the hot state on sintered glass. The filtrate was taken up in 50-cm3 of ethyl acetate and concentrated to dryness under reduced pressure (5 kPa). The residue was taken up in 75-cm3 of ethyl acetate and 40-cm3 of water. The organic phase was separated after settling out, washed twice with 40-cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue was purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ; diameter 2.5 cm; height 40 cm), eluting with a mixture of cyclohexane-ethyl acetate (75/25 by volume) and collecting 50-cm3 fractions. Fractions 16 to 22 were combined and then concentrated. 1,77 g of methyl (3RS,4RS)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-propyl]-1-(tert-butyloxycarbonyl)piperidine-3-carboxylate were obtained in the form of a colorless oil.

Provenance & Evidence