4-Bromoanisole → HCID 11360273, compound

Participants

Reaction Conditions

Reaction Steps

Twelve liters of 1,4-dioxane were vacuum degassed and then combined with sodium tert-butoxide (1523 g, 15.84 mol), 4-bromoanisole (1845 g, 9.86 mol) and 3,4-dihydro-6-(phenylmethoxy)-1(2H)-naphthalenone (1002 g, 3.97 mol). The resulting red slurry was again degassed by pulling vacuum and purging the system with nitrogen. Palladium acetate (8.90 g, 0.0396 mol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (25.9 g, 0.0416 mol) were added and the mixture was heated to 70° C. After 2.5 hours the temperature was increased to 100° C. and this temperature was maintained for an additional 5 hours. The mixture was allowed to cool to ambient temperature before quenching with 6 liters of 3 M HCl. The layers were allowed to separate and the aqueous phase was extracted with 2 liters of ethyl acetate. The organic phases were combined and dried with 500 g of sodium sulfate then concentrated to a red solid. The solid was combined with 4 liters of toluene and stirred at 60° C. for 1 hour then cooled to ambient temperature. The solids were collected by filtration, washed with toluene and dried in vacuo to provide 564 g (40%) of the title compound. H1 NMR (CDCl3, 500 MHz) 8.20 (d, J=9.1 Hz, 1H), 7.50 (d, J=7.3 Hz, 2H), 7.44 (d, J=8.7 Hz, 2H), 7.42 (t, J=7.3 Hz, 2H), 7.35 (m, 2H), 7.29 (d, J=8.5 Hz, 1H), 7.25 (dd, J=2.5, 9.1 Hz, 1H), 7.20 (d, J=2.5, 1H), 7.07 (d, J=8.7 Hz, 2H), 5.75 (s, 1H), 5.20 (s, 2H), 3.88 (s, 3H).

Provenance & Evidence