反应详情

To a solution of 5-bromo-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 54b (1.03 g, 3.0 mmol) in acetonitrile (20 mL) and triethylamine (12.5 mL) was added 4-vinylpyridine (0.65 mL, 6 mmol), palladium acetate (125 mg, 0.56 mmol) and tri-o-tolylphosphine (625 mg). The mixture was heated at reflux for 16 hours. The solvent was removed, and the residue was washed with saturated sodium bicarbonate was added to free the amine, and the mixture was extracted with EtOAc, dried (MgSO4), and concentrated. The residue was chromatographed on a silica gel column, eluting with hexane:Et2O 1:2 to 0:1 to afford the title compound (760 mg, 69%). MS (CI/NH3) m/z 368 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.43 (s, 9H), 2.35 (m, 2H), 3.90 (m, 2H), 4.20 (m, 1H), 4.40 (m, 1H), 4.55 (m, 1H), 7.10 (m, 1H), 7.2 (m, 1H), 7.38 (m, 2H), 7.45 (br s, 1H), 8.29 (m, 1H), 8.37 (s, 1H), 8.61 (m, 2H).

1. temperatureThe mixture was heated
2. temperatureat reflux for 16 hours
3. customThe solvent was removed
4. washthe residue was washed with saturated sodium bicarbonate
5. additionwas added
6. extractionthe mixture was extracted with EtOAc
7. dry with materialdried (MgSO4)
8. concentrationconcentrated
9. customThe residue was chromatographed on a silica gel column
10. washeluting with hexane:Et2O 1:2 to 0:1