反应详情

Add a solution of isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.080 g, 0.134 mmol) in tetrahydrofuran (1 mL) to phenylboronic acid (0.024 g, 0.202 mmol), palladium acetate (0.0015 g, 0.0067 mmol), 2-(dicyclohexylphosphino)biphenyl (0.0047 g, 0.013 mmol) and potassium fluoride (0.023 g, 0.403 mmol) and purge with nitrogen and stir for 2 h at room temperature, then at 50° C. for 12 h. After this initial period, additional phenylboronic acid (0.024 g, 0.202 mol), palladium acetate (0.0015 g, 0.0067 mmol), 2-(dicyclohexylphosphino)biphenyl (0.0047 g, 0.013 mmol) and potassium fluoride (0.023 g, 0.403 mmol) is added and the reaction is heated at 50° C. for 1 h. Cool the reaction to room temperature and dilute with ethyl acetate (30 mL) and wash with 2 N sodium hydroxide and brine (10 mL each). Dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as a white solid (0.058 g, 72%): ESI MS 593 (M+H).

1. custompurge with nitrogen
2. waitat 50° C. for 12 h
3. temperaturethe reaction is heated at 50° C. for 1 h
4. temperatureCool
5. customthe reaction to room temperature
6. washwash with 2 N sodium hydroxide and brine (10 mL each)
7. dry with materialDry the organic layer over sodium sulfate
8. filtrationfilter
9. customremove the solvent under reduced pressure
10. customPurify the residue
11. washeluting with hexanes/ethyl acetate (60:40)