Sodium Carbonate → 1,1-Dimethylethyl (2S)-4-[(3'-cyano-4'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

Participants

Reaction Steps

To a solution of (3-cyano-4-fluorophenyl)boronic acid (0.983 g, 5.96 mmol) in DME (40 mL) was added 1,1-dimethylethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylate (2.20 g, 5.96 mmol) followed by Na2CO3 (17 mL, 2M in H2O, 34.0 mmol). The reaction vessel was flushed with Ar, and tetrakis(triphenylphosphine)palladium(0) (2.06 g, 1.78 mmol) was added. The reaction mixture was placed in an oil bath at 78° C. under Ar for overnight. The reaction was diluted with EtOAc (600 mL) and washed with H2O (250 mL). The water layer was extracted with EtOAc (1×100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. Purification of the crude residue by flash chromatography (20% EtOAc/80% hexane) on silica gel gave the title compound (1.77 g, 73.1%). EI-MS m/z 410 (M−H)+.

Provenance & Evidence