1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-Cyclopentyl-2-hydroxy-2-phenyl-1-piperazin-1-ylethanone

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). DIPEA (23.7 mL, 13.6 mmol) and HOBt (10.4 g, 68.1 mmol) were added to the mixture, followed by 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), and then saturated aqueous NaCl (300 mL). The organic layer was dried over MgSO4 and filtered. The solvent was removed by rotary evaporation. 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 by rotary evaporation. 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 by silica gel chromatography (10% MeOH/DCM with 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. dry with materialThe organic layer was dried over MgSO4
3. filtrationfiltered
4. customThe solvent was removed by rotary evaporation
5. additionA solution of 20% TFA/DCM was added to the crude material
6. stirringthe resulting mixture was stirred for 2 hours at room temperature
7. customThe solvent was removed by rotary evaporation
8. additionDCM (300 mL) was added
9. washthe mixture was washed with saturated sodium bicarbonate (300 mL)
10. customThe organic layer was then 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))

ORD record

ord-7be8cedd43bd4ca398ab8b7495ddbbcb

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242138B2