反应详情

温度

67 °C

To the crude product of the previous step was added THF (420 mL) and the solution was purged with nitrogen for 5 min. To a 2 L flask was added 3-carbamoylphenyl boronic acid (98%, 33.0 g, 200 mmol), palladium (II) acetate (98%. 0.46 g, 2 mmol), 1,1′-bis(diphenylphosphino)ferrocene (97%, 1.1 g, 2 mmol). and potassium fluoride (34.9 g, 600 mmol) followed by the THF solution of trifluoro-methanesulfonic acid 8-benzyl-8-aza-bicyclo[3.2.1]oct-2-en-3-yl ester. The resulting mixture was purged with nitrogen for 5 min, heated to reflux (67° C.) under nitrogen and stirred for 2 h. The reaction mixture was cooled to 30° C., then EtOAc (500 mL) and 1 N NaOH (500 mL) were added and the mixture was stirred at 22° C. for 10 min. The layers were separated and the aqueous layer was discarded. The organic layer was washed with a mixture of brine (250 mL) and water (250 mL) and stirred for 5 min. The layers were separated and the aqueous layer was discarded. The organic layer was briefly dried over Na2SO4, filtered, and solvent was partially removed. Product precipitated as light yellow solids during solvent removal. The resulting slurry (about 200 mL) was filtered and the solids were washed with cold EtOAc (0° C., 100 mL) and dried under high vacuum at 25° C. to provide the title intermediate (42.5 g) as a light yellow solid.

1. customthe solution was purged with nitrogen for 5 min
2. customThe resulting mixture was purged with nitrogen for 5 min
3. temperatureheated
4. temperatureThe reaction mixture was cooled to 30° C.
5. additionEtOAc (500 mL) and 1 N NaOH (500 mL) were added
6. stirringthe mixture was stirred at 22° C. for 10 min
7. customThe layers were separated
8. washThe organic layer was washed with a mixture of brine (250 mL) and water (250 mL)
9. stirringstirred for 5 min
10. customThe layers were separated
11. dry with materialThe organic layer was briefly dried over Na2SO4
12. filtrationfiltered
13. customsolvent was partially removed
14. customProduct precipitated as light yellow solids during solvent removal
15. filtrationThe resulting slurry (about 200 mL) was filtered
16. washthe solids were washed with cold EtOAc (0° C., 100 mL)
17. customdried under high vacuum at 25° C.