Sodium Carbonate → [2-(2,4-Difluoro-phenyl)-6-methoxynaphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

Participants

Reaction Steps

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (12.4 g, 23.0 mmol) and 2,4-difluorophenylboronic acid (7.0 g, 46.0 mmol) in degassed dimethoxyethane (620 mL). Add 2M aqueous sodium carbonate (73 mL, 145 mmol) and stir at room temperature under nitrogen for 5 minutes. Add palladium(II) acetate (520 mg, 2.3 mmol) and triphenylphosphine (1.2 g, 4.6 mmol) and plunge into a 85° C. oil bath. Stir for 40 minutes and cool to room temperature. Pour into saturated aqueous sodium bicarbonate and extract twice with methylene chloride. Dry the combined organic layers with sodium sulfate, filter and concentrate in vacuo. Purify the resultant oil with SCX columns (load in methanol, elute with 2M NH3/MeOH) to yield 10.8 g (93%) of the title compound: mass spectrum (ion spray) m/z=502.3 (M+H).

Provenance & Evidence