反应详情

Under a nitrogen atmosphere, a 50-liter flask is charged with compound 5 (1.735 kg, 3.304 mol) prepared from Example 3 in 2-methyl-THF, boronic acid 6 (0.877 kg, 5.617 mol), PdCl2(PPh3)2 (0.116 kg, 0.165 mol) and an aqueous sodium bicarbonate (0.833 kg, 9.912 mol) solution (8.7 L). The reaction mixture is degassed and heated to reflux for 7 hrs and stirred at room temperature overnight. Compound 6 (129.0 g) and PdCl2(PPh3)2 (6.6 g) are added again and the reaction mixture is heated to reflux for another 5 hrs. Celite (1.735 kg) is added and the mixture is stirred for 30 minutes and then filtered through a pad of celite. The residue is washed with 2-methyl-THF. The organic layer is separated, washed with a 10% NaCl aqueous solution (4 L) for three times, further washed with a 20% NaCl aqueous solution, filtered, and dried over Na2SO4. The filtrate is concentrated by removing about 80-85% of solvent, added ethyl acetate (3.5 L) and stirred overnight. The mixture is filtered and washed with ethyl acetate (2×3.5 L) twice. Compound 7, is isolated after removing the solvents and drying at 45° C. for 48 hrs (2.765 kg, 74% yield).

1. customThe reaction mixture is degassed
2. temperatureheated
3. temperatureto reflux for 7 hrs
4. additionCompound 6 (129.0 g) and PdCl2(PPh3)2 (6.6 g) are added again
5. temperaturethe reaction mixture is heated
6. temperatureto reflux for another 5 hrs
7. additionCelite (1.735 kg) is added
8. stirringthe mixture is stirred for 30 minutes
9. filtrationfiltered through a pad of celite
10. washThe residue is washed with 2-methyl-THF
11. customThe organic layer is separated
12. washwashed with a 10% NaCl aqueous solution (4 L) for three times
13. washfurther washed with a 20% NaCl aqueous solution
14. filtrationfiltered
15. dry with materialdried over Na2SO4
16. concentrationThe filtrate is concentrated
17. customby removing about 80-85% of solvent
18. additionadded ethyl acetate (3.5 L)
19. stirringstirred overnight
20. filtrationThe mixture is filtered
21. washwashed with ethyl acetate (2×3.5 L) twice