反应详情

温度

22.5 °C

A 50 L reactor was charged with 3-hydroxyphenylboronic acid (1.776 kg, 12.88 mol, 1.05 eq), 3-bromobenzamide (2.453 kg, 12.26 mol, 1.0 eq), tetrabutylammonium bromide (0.198 kg, 0.61 mol, 0.05 eq), PdCl2 (0.011 kg, 0.061 mol, 0.005 eq), and EtOH (9.689 kg). To the reaction mixture at 20-25° C., with moderate stirring, was added a slurry of K2CO3 (3.390 kg, 24.53 mol, 2 eq) in EtOH (4.84 kg). The K2CO3 container was rinsed with EtOH (4.84 kg) into the reactor. The reaction mixture was stirred at 20-25° C. for approximately 3-5 hours and monitored by thin layer chromatography (TLC) (hexanes:EtOAc 6:4). After the reaction was judged to be complete, 10% aq. HCl was added to the reaction mixture until the pH reached 1-2. Additional 10% aq. HCl was added, resulting in a final pH less than 1. The solution was agitated for approximately 35 minutes at 20-25° C. Approximately 12 liters of the solution was drained off and set aside. The remaining reaction mixture was diluted with EtOAc and washed with water (0.17 mL of EtOAc was added per mL of solution, and 0.294 mL of water per mL of solution). The organic phases were combined and concentrated in vacuo. Once the organic phases were reduced in volume to about 9 L, the mixture was transfered to reactor and 32 L of water was added. The temperature of the mixture was adjusted to 0-5° C., and it was agitated for 30 minutes. The product precipitated from the mixture and was filtered. The filter cake was washed with water from the reactor and dried at ambient temperature for about 18 hours, yielding 2.212 Kg (85%) of a white solid.

1. washThe K2CO3 container was rinsed with EtOH (4.84 kg) into the reactor
2. addition10% aq. HCl was added to the reaction mixture until the pH
3. additionAdditional 10% aq. HCl was added
4. customresulting in a final pH less than 1
5. stirringThe solution was agitated for approximately 35 minutes at 20-25° C
6. customThe remaining reaction mixture
7. washwashed with water (0.17 mL of EtOAc was added per mL of solution, and 0.294 mL of water per mL of solution)
8. concentrationconcentrated in vacuo
9. customthe mixture was transfered to reactor
10. addition32 L of water was added
11. customwas adjusted to 0-5° C.
12. stirringit was agitated for 30 minutes
13. customThe product precipitated from the mixture
14. filtrationwas filtered
15. washThe filter cake was washed with water from the reactor
16. customdried at ambient temperature for about 18 hours