Cesium fluoride → [6-Hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

참여 물질

반응 조건

반응 단계

Dissolve trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (10.0 g, 16.6 mmol) in degassed acetonitrile (100 mL). Add cesium fluoride (13.0 g, 83 mmol) and bis(acetato)bis(triphenylphosphine)palladium (1.2 g, 1.7 mmol) followed by bis(neopentyl glycolato)diboron (4.5, 19.9 mmol) and plunge into a 75° C. oil bath under nitrogen. After 15 minutes, add 1-bromo-2,3,5-trifluorobenzene (7.0 g, 33.2 mmol) to the reaction and bis(acetato)bis(triphenylphosphine)palladium (500 mg) and stir at 75° C. for 2.5 hours. Cool the reaction to room temperature and filter through celite. Concentrate the filtrate in vacuo and redissolve the residue in methanol (100 mL). Add KOH (4 g) and stir at room temperature overnight. Pour the reaction into saturated aqueous ammonium chloride and extract with methylene chloride. Dry the organic layer with sodium sulfate, filter and concentrate in vacuo. Purify on 5 SCX columns (loading with methanol and eluting with 2M NH3 in methanol) to obtain 8.4 g (100%) of the title compound. Mass spectrum (ion spray): m/z=506.4 (M+H).

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