反应详情

To a mixture of 192 mg of tert-butyl {[4-(2-fluorophenyl)piperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate and 157 mg of sodium hydrogen carbonate were added 3 mL of THF and 1.5 mL of water, followed by addition of 133 mg of methyl 4-[(chlorocarbonyl)oxy]benzoate (Fluka). It was stirred at room temperature for 1 hour, and then extracted with ethyl acetate. The organic layer was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and to 327 mg of the obtained residue were added 4 mL of THF, 2 mL of methanol, and 2.5 mL of a 1 M aqueous sodium hydroxide solution, followed by stirring at room temperature overnight. The reaction mixture was neutralized by addition of 2.6 mL of 1 M hydrochloric acid, concentrated under reduced pressure, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 228 mg of 4-({[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(2-fluorophenyl)piperidin-1-yl]carbonyl}oxy)benzoic acid as a colorless foamy substance. ESI+: 627

1. extractionextracted with ethyl acetate
2. washThe organic layer was washed with water and saturated brine in this order
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationAfter filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. additionto 327 mg of the obtained residue were added 4 mL of THF, 2 mL of methanol, and 2.5 mL of a 1 M aqueous sodium hydroxide solution
7. stirringby stirring at room temperature overnight
8. additionThe reaction mixture was neutralized by addition of 2.6 mL of 1 M hydrochloric acid
9. concentrationconcentrated under reduced pressure
10. extractionextracted with ethyl acetate
11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe obtained residue was purified by silica gel column chromatography (chloroform-methanol)