反应详情

To a stirred solution of (R)-cyclopentylhydroxyphenyl acetic acid (1.0 g, 4.54 mmol) in DCM (50 mL) was added t-butoxycarbonyl-4-aminopiperidine (0.9 g, 4.5 mmol). DIPEA (2.4 mL, 1.4 mmol) and HOBt (1.0 g, 6.8 mmol) were added to the mixture, followed by EDCI (1.0 g, 5.5 mmol). The mixture was stirred at room temperature for 12 hours. The mixture was then washed with 1N NaOH (50 mL), 1N HCl (50 mL), and then saturated aqueous NaCl (50 mL). The organic layer was dried over MgSO4 and filtered. The solvent was removed by rotary evaporation. To the crude material was added a solution of 20% TFA/DCM and the reaction was stirred for 2 hours at room temperature. The solvent was removed by rotary evaporation. DCM (50 mL) was added and the mixture was then washed with saturated sodium bicarbonate (50 mL). The organic layer was removed, dried over MgSO4 and filtered. The crude material was purified by silica gel chromatography (10% MeOH/DCM with 1% NH3 (aq)) to afford the title compound as a white powder (920 mg, 3.0 mmol).

1. washThe mixture was then washed with 1N NaOH (50 mL), 1N HCl (50 mL)
2. dry with materialThe organic layer was dried over MgSO4
3. filtrationfiltered
4. customThe solvent was removed by rotary evaporation
5. additionTo the crude material was added a solution of 20% TFA/DCM
6. stirringthe reaction was stirred for 2 hours at room temperature
7. customThe solvent was removed by rotary evaporation
8. additionDCM (50 mL) was added
9. washthe mixture was then washed with saturated sodium bicarbonate (50 mL)
10. customThe organic layer was removed
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. customThe crude material was purified by silica gel chromatography (10% MeOH/DCM with 1% NH3 (aq))