Water → HCID 66906192, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 300 mg of tert-butyl {[4-(3-fluorophenyl)piperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate in 3.0 mL of toluene was added 0.136 mL of triethylamine and 149 mg of ethyl 4-isocyanatobenzoate at room temperature, followed by stirring at 100° C. for 2 days. The reaction mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and to the obtained residue were added 8 mL of THF, 4 mL of methanol, and 4 mL of a 1 M aqueous sodium hydroxide solution, followed by stirring at room temperature for 24 hours. The reaction mixture was neutralized by addition of 4.1 mL of 1 M hydrochloric acid, then concentrated under reduced pressure, and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 356 mg of 4-({[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(3-fluorophenyl)piperidin-1-yl]carbonyl}amino)benzoic acid as a colorless foamy substance. ESI+: 626

Provenance & Evidence