反应详情

To a stirred solution of (R)-cyclopentylhydroxyphenyl acetic acid (10.0 g, 45.4 mmol) in DCM (200 mL) was added t-butyl 1-piperazinecarboxylate (8.5 g, 45.4 mmol). Into the reaction was added DIPEA (23.7 mL, 13.6 mmol), HOBt (10.4 g, 68.1 mmol), and then EDCI (10.4 g, 54.5 mmol). The mixture was stirred at room temperature for 12 hours. The mixture was then washed with 1N NaOH (300 mL), 1N HCl (300 mL) then saturated aqueous NaCl (300 mL). The organic layer was then removed, dried over MgSO4 and then filtered. The solvent was removed under reduced pressure. A solution of 20% TFA/DCM was added to the crude material, and the resulting mixture was stirred for 2 hours at room temperature. The solvent was removed under reduced pressure. DCM (300 mL) was added and the mixture was washed with saturated sodium bicarbonate (300 mL). The organic layer was then removed, dried over MgSO4 and filtered. The crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq)) to afford the title compound as a white powder (9.0 g, 31.2 mmol).

1. washThe mixture was then washed with 1N NaOH (300 mL), 1N HCl (300 mL)
2. customThe organic layer was then removed
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. customThe solvent was removed under reduced pressure
6. additionA solution of 20% TFA/DCM was added to the crude material
7. stirringthe resulting mixture was stirred for 2 hours at room temperature
8. customThe solvent was removed under reduced pressure
9. additionDCM (300 mL) was added
10. washthe mixture was washed with saturated sodium bicarbonate (300 mL)
11. customThe organic layer was then removed
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. customThe crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq))