Ethanol → HCID 136348244, compound

Participants

Reaction Steps

To a mixture of 183 mg of tert-butyl {[1-(4-cyano-2,6-difluorophenyl)-3-phenylpiperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate obtained in Example 53 (1), 44 mg of hydroxylamine hydrochloride, and 2 mL of ethanol was added 0.088 mL of triethylamine, and the mixture was stirred for 4 hours while heating under reflux. The mixture was left to be cooled to room temperature, and water was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. This was filtered, and the filtrate was then concentrated under reduced pressure to obtain a residue (colorless foamy substance, 233 mg). To this residue were added 2 mL of DMF and 0.033 mL of pyridine, the mixture was cooled in an ice bath, and then 0.061 mL of 2-ethylhexyl chloroformate was added thereto, followed by stirring for 1 hour while keeping cooling on ice. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine in this order, and the organic layer was then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, to the obtained residue was added 2 mL of xylene, and the mixture was stirred for 5 hours while heating under reflux. This was left to be cooled to room temperature, and then purified by silica gel column chromatography (chloroform/methanol) to obtain 184 mg of tert-butyl ({1-[2,6-difluoro-4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]-3-phenylpiperidin-4-yl}methyl)[(1R)-1-(1-naphthyl)ethyl]carbamate as a yellow foamy substance. ESI+: 641

Provenance & Evidence