反应详情

温度

-70 °C

Combine 7-bromobenzo[b]thiophene (300 g, 1.41 mmol) and tri-isopropylborate (403.6 g, 2.15 mmol) in anhydrous THF (4 L) in a 12-L Morton flask fitted with a mechanical stirrer and cool under nitrogen in a dry-ice/acetone bath to −70° C. Add n-butyl lithium (1.6 M in hexane, 714 g, 1.68 mmol) dropwise at such a rate as to keep the internal temperature less than −67.5° C. After the addition is complete allow the reaction mixture to stir at this temperature for 1 h. Remove the cooling bath and slowly add 4 L of water, which causes the temperature to rise to about −5° C. Next, add concentrated HCl (75 mL) until the pH of the solution is about pH=2. Allow the slurry to stir for 1 h. Add sufficient 5 N aqueous NaOH to adjust the pH of the mixture to about pH=12 and transfer to a 22-L bottom-drop funnel Separate and save the lower aqueous layer. Dilute the upper organic layer with 4 L of methyl-tert-butyl ether and extract with 1 L of 5 N aqueous NaOH. Separate the aqueous layer, combine with the previous aqueous extract and place back in the separatory funnel Wash the aqueous layer with additional methyl-tert-butyl ether (4 L). Again, separate the aqueous layer and transfer to a 12-L, 3-neck round bottom flask fitted with a mechanical stirrer. Cool the solution to +5° C. with an ice-water bath. Add concentrated HCl slowly until the pH of the solution is about pH=2. Stir the mixture for 30 minutes and then filter off the resulting solid. Rinse the solid on the funnel twice with 2 L of water and allow to air-dry for 30 min. Place the solid in a vacuum oven at 50° C. and dry under vacuum overnight. The dried solid is slurried with 2 L of n-heptane for 30 min to remove the yellow color. Again filter off the solid, air-dry for 30 min and then vacuum-dry at 40° C. overnight to give the title compound (188.8 g, 75%) as a white solid. 1H NMR (400 MHz, CD3OD) δ 7.86 (d, J=8 Hz, 1H), 7.49-7.57 (m, 2H), 7.30-7.39 (m, 2H).

1. customthe internal temperature less than −67.5° C
2. additionAfter the addition
3. customRemove the cooling bath and slowly add 4 L of water, which
4. customto rise to about −5° C
5. additionNext, add concentrated HCl (75 mL) until the pH of the solution
6. stirringto stir for 1 h
7. additionAdd sufficient 5 N aqueous NaOH
8. customSeparate
9. additionDilute the upper organic layer with 4 L of methyl-tert-butyl ether
10. extractionextract with 1 L of 5 N aqueous NaOH
11. customSeparate the aqueous layer
12. extractionaqueous extract
13. washWash the aqueous layer with additional methyl-tert-butyl ether (4 L)
14. customAgain, separate the aqueous layer and transfer to a 12-L, 3-neck round bottom flask
15. customfitted with a mechanical stirrer
16. temperatureCool the solution to +5° C. with an ice-water bath
17. additionAdd concentrated HCl slowly until the pH of the solution
18. stirringStir the mixture for 30 minutes
19. filtrationfilter off the resulting solid
20. washRinse the solid on the funnel twice with 2 L of water
21. customto air-dry for 30 min
22. customat 50° C.
23. customdry under vacuum overnight
24. waitThe dried solid is slurried with 2 L of n-heptane for 30 min
25. customto remove the yellow color
26. filtrationAgain filter off the solid
27. customair-dry for 30 min
28. customvacuum-dry at 40° C. overnight