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

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Reaction Steps

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).

Provenance & Evidence