1-Methylpiperazine → 4-(4-Methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamine

Participants

Reaction Steps

Pd2(dba)3 (1.1 g, 1.2 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (0.94 g, 2.4 mmol), 5-bromo-2-trifluoromethoxy-phenylamine (30.7 g, 120 mmol) in THF (50 mL) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1M in THF, 288 mL) and N-methylpiperazine (26.7 mL, 194 mmol) were added and the reaction refluxed for 1 hours. The reaction mixture was then allowed to cool to room temperature and filtered through a pad of celite. The organic phase was concentrated, the residue dissolved in DCM (200 mL) and washed with H2O (1×100 mL). The organic phases were dried over anhydrous Na2SO4, the solvent evaporated in vacuo and the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 23 g of 4-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamine (70% yield) as a light brown powder.

Provenance & Evidence