反应详情

A mixture of 11 (3.7 g, 8.94 mmol, 1.0 equiv), 2-bromopyridine (1.6 g, 0.95 mL, 10 mmol, 1.12 equiv), K2CO3 (3.7 g, 26.8 mmol, 3.0 equiv), dioxane (60 mL) and H2O (10 mL) was degassed with N2 for 5 min. Pd(Ph3P)4 (0.5 g, 0.43 mmol, 4.8 mole %) was added and the mixture refluxed for 8 hr, cooled to room temperature and stirred for 48 hr. The reaction suspension was diluted with EtOAc (100 mL) and the mixture filtered through Celite, washing the Celite pad with EtOAc (100 mL). The filtrate was concentrated under reduced pressure giving a yellow oil. The oil was partitioned between 1:1 EtOAc/heptanes (100 mL) and H2O (50 mL). The organic phase was washed with H2O (3×50 mL), brine (50 mL), dried over Na2SO4, filtered and the solution concentrated under reduced pressure to give a colorless oil. The crude product was absorbed onto silica gel using DCM and dry-loaded on a column of silica gel (50 g) packed in hexanes. The column was eluted with hexanes (800 mL), 3% EtOAc/hexanes (500 mL), 6% EtOAc/hexanes (500 mL), 10% EtOAc/hexanes (500 mL), and 15% EtOAc/hexanes (500 mL). Product fractions (eluted with 15% EtOAc/hexanes) were concentrated under reduced pressure yielding an oil that crystallized on pumping under high vacuum to give 1.46 g (42%) of 7 as a white solid.

1. customwas degassed with N2 for 5 min
2. temperaturethe mixture refluxed for 8 hr
3. filtrationthe mixture filtered through Celite
4. washwashing the Celite pad with EtOAc (100 mL)
5. concentrationThe filtrate was concentrated under reduced pressure
6. customgiving a yellow oil
7. customThe oil was partitioned between 1:1 EtOAc/heptanes (100 mL) and H2O (50 mL)
8. washThe organic phase was washed with H2O (3×50 mL), brine (50 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationthe solution concentrated under reduced pressure
12. customto give a colorless oil
13. customThe crude product was absorbed onto silica gel
14. washThe column was eluted with hexanes (800 mL), 3% EtOAc/hexanes (500 mL), 6% EtOAc/hexanes (500 mL), 10% EtOAc/hexanes (500 mL), and 15% EtOAc/hexanes (500 mL)
15. washProduct fractions (eluted with 15% EtOAc/hexanes)
16. concentrationwere concentrated under reduced pressure
17. customyielding an oil that
18. customcrystallized