Piperazine → 1-(4-Benzyloxy-3-fluorophenyl)piperazine

Temperature

110 °C

sodium 2-methylpropan-2-olate (6.43 g, 66.88 mmol) was added to 1-(benzyloxy)-4-bromo-2-fluorobenzene (13.43 g, 47.77 mmol) and piperazine (24.69 g, 286.64 mmol) in toluene (140 mL). The resulting mixture was bubbled with nitrogen for 10 minutes then 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (2.97 g, 4.78 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (1.094 g, 1.19 mmol) were added and the mixture was stirred at 110 °C for 20 hours. The reaction mixture was cooled to room temperature then fitered through celite and the filter cake washed with ethyl acetate (500 mL). The filtrate was evaporated to give crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in DCM. Pure fractions were evaporated to dryness to afford 1-(4-(benzyloxy)-3-fluorophenyl)piperazine (9.80 g, 71.6 %) as a solid.

ORD record

ord-996b98cdf02a43a3b340c4e4f981f563

Source dataset

750 AstraZeneca ELN dataset

Original link

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