4-Bromophenol → 4-(4-Methyl-1-piperazinyl)phenol

Participants

Reaction Conditions

Reaction Steps

diacetoxypalladium (0.039 g, 0.17 mmol) was added in one portion to 4-bromophenol (3 g, 17.34 mmol) and 1-methylpiperazine (2.308 mL, 20.81 mmol) in toluene (87 mL) at 25°C under nitrogen. To this was added toluene (87 mL) then a solution of 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (0.123 mL, 0.35 mmol) in Toluene (1 mL) and finally 1M LITHIUM BIS(TRIMETHYLSILYL)AMIDE (39.9 mL, 39.88 mmol) in THF was added dropwise over 1 minute. The resulting mixture was stirred at 80 °C for 18 hours. The reaction was allowed to cool to room temperature, SiO2 (23g) was added and evaporated to dryness. The crude product was purified by flash silica chromatography (120g), elution gradient 0 to 10% MeOH in EtOAc. Pure fractions were evaporated to dryness to afford 4-(4-methylpiperazin-1-yl)phenol (1.700 g, 51.0 %) as a beige solid.

Provenance & Evidence