Triphenylphosphine → (R)-benzyl 2-(4-cyano-3-(trifluoromethyl)phenyl)-3-oxo-hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

To (S)-benzyl 3-(hydroxymethyl)piperazine-1-carboxylate (256 mg, 1.02 mmol) in DMA (1 mL) was added phenyl 4-cyano-3-(trifluoromethyl)phenylcarbamate (250 mg, 0.82 mmol), and the mixture was heated to 40° C. for 5 h. The reaction was cooled to RT, and PPh3 (321 mg, 1.22 mmol) followed by DIAD (241 μL, 1.22 mmol) were added to the reaction. After stirring for 15 min at RT, the reaction was diluted with EtOAc (20 mL) and washed twice with 0.5 N NaOH (10 mL), then twice with sat'd brine (10 mL). The EtOAc was dried over MgSO4 then concentrated in vacuo. The residue was taken up in CH2Cl2 (5 mL) and cooled to −10° C., and Et2O (5 mL) was added. The resulting precipitate was collected by filtration and rinsed with cold 1:1 Et2O:CH2Cl2 to give Example 1, (R)-benzyl 2-(4-cyano-3-(trifluoromethyl)phenyl)-3-oxo-hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxylate 187 mg (52%). HPLC RT: 3.253 min (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous MeOH over 4 minutes containing 0.1% TFA, 4 ml/min, monitoring at 220 nm). (M+H)+:445.

Provenance & Evidence