Dichloromethane → Tert-butyl 4-{4'-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)methyl][1,1'-biphenyl]-4-yl}-1-piperazinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To 2-[(4-bromobenzyl)oxy]-N-(cyanomethyl)-4-methylpentanamide (646 mg, 1.9 mmoles) in DMF (12.5 mL) was added 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (640 mg, 2.1 mmoles) followed by 2 M aqueous sodium carbonate (2.85 mL, 5.7 mmoles) and finally [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (78 mg, 0.1 mmoles). The reaction was stirred overnight at 85° C. and cooled to room temperature prior to taking it up in ethylacetate. The organic phase was washed three times with 1.2 N hydrochloric acid, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography (10% EtOAc, 90% Hexanes) to give tert-butyl 4-{4′-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)-methyl][1,1 ′-biphenyl]-4-yl}-1-piperazinecarboxylate.

Provenance & Evidence