反应详情

温度

75 °C

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).

1. temperatureCool
2. customthe reaction to room temperature
3. filtrationfilter through celite
4. concentrationConcentrate the filtrate in vacuo
5. dissolutionredissolve the residue in methanol (100 mL)
6. stirringAdd KOH (4 g) and stir at room temperature overnight
7. additionPour
8. customthe reaction into saturated aqueous ammonium chloride
9. extractionextract with methylene chloride
10. dry with materialDry the organic layer with sodium sulfate
11. filtrationfilter
12. concentrationconcentrate in vacuo
13. customPurify on 5 SCX columns (loading with methanol and eluting with 2M NH3 in methanol)