Methoxymethyl-triphenylphosphonium chloride → 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-3-(2-hydroxyethyl)quinolin-4(1H)-one

Participants

Reaction Steps

428 mg of (methoxymethyl)triphenylphosphonium chloride was dissolved in 5 ml of THF, and 1.2 ml of 1.6 M n-butyl lithium hexane solution was added under ice-cooling in an atmosphere of argon, followed by stirring at the same temperature for 30 minute. A 5 ml THF solution of 178 mg of 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbaldehyde was added under ice-cooling thereto, followed by stirring at the same temperature for 15 minutes and then stirring at room temperature for 3 hours. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate, drying over anhydrous sodium sulfate and then concentration under a reduced pressure. The resulting residue was dissolved in 10 ml of dioxane, and 5 ml of a 4 M hydrogen chloride dioxane solution was added, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into an ice-cooled aqueous saturated sodium hydrogen carbonate, followed by extraction with ethyl acetate, drying over anhydrous sodium sulfate and then concentration under a reduced pressure. By purifying the resulting residue by silica gel column chromatography, 239 mg of crude product of [7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]acetaldehyde was obtained. The resulting crude product was dissolved in 10 ml of ethanol, and 75 mg of sodium borohydride was added, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate, drying over anhydrous sodium sulfate and then concentration under a reduced pressure. The resulting residue was purified by silica gel column chromatography and crystallized from ethyl acetate to obtain 18 mg of 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-3-(2-hydroxyethyl)quinolin-4(1H)-one.

Provenance & Evidence