Toluene → tert-Butyl 4-(3-formyl-4-hydroxyphenyl)piperazine-1-carboxylate

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Reaction Steps

0.58 g of bis(dibenzylideneacetone)palladium and 0.16 g of tri-tert-butylphosphine are added under nitrogen to 200 ml of toluene, and the resultant solution, which becomes dark red, is stirred at 20° for 30 minutes. 10 g of 5-bromo-2-hydroxybenzaldehyde, 10.2 g of tert-butyl 1-piperazinecarboxylate and 7.2 g of sodium tert-butoxide are then added. The mixture is stirred at 60° for 24 hours and cooled, 800 ml of water are added, and the mixture is extracted with 2×500 ml of ethyl acetate. The organic phases are combined and washed with 300 ml of water, and the solvent is removed at 30° under reduced pressure. The dark-orange oil which remains (11 g) is purified by chromatography (300 g of silica gel; MTB ether/heptane 5:1; 1.5 litres) leaving 7.8 g of pale-yellow crystals (51%), m.p. 84-86°; MS 306 (M+), 250 (100%), 233, 176, 164.

Provenance & Evidence