Triisopropyl borate → 1-Benzothien-7-ylboronic acid

Temperature

-70 °C

Combine 7-bromobenzo[b]thiophene (300 g, 1.41 mmol) and triisopropylborate (403.6 g, 2.15 mmol) in anhydrous tetrahydrofuran (THF) (4000 mL) 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 hour. Remove the cooling bath and slowly add 4 L of water. Next, add concentrated HCl (75 mL) until the pH of the solution is about pH=2. Allow the slurry to stir for 1 hour. Add sufficient 5 N aqueous NaOH to adjust the pH of the mixture to about pH=12. Separate the layers and save the aqueous layer. Dilute the organic layer with 4 L of methyl-tert-butyl ether and extract with 1 L of 5 N aqueous NaOH. Separate the layers. Combine the aqueous layer with the previous aqueous extract. Wash the aqueous layer with additional methyl-tert-butyl ether (4 L). Separate the layers and transfer the aqueous layers 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 min and 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. Remove the yellow color by slurrying the dried solid with 2 L of n-heptane for 30 min. Again filter off the solid, air-dry for 30 min, and vacuum dry at 40° C. overnight to afford 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
4. additionNext, add concentrated HCl (75 mL) until the pH of the solution
5. stirringto stir for 1 hour
6. additionAdd sufficient 5 N aqueous NaOH
7. customSeparate the layers
8. additionDilute the organic layer with 4 L of methyl-tert-butyl ether
9. extractionextract with 1 L of 5 N aqueous NaOH
10. customSeparate the layers
11. washWash the aqueous layer with additional methyl-tert-butyl ether (4 L)
12. customSeparate the layers
13. customfitted with a mechanical stirrer
14. temperatureCool the solution to +5° C. with an ice-water bath
15. additionAdd concentrated HCl slowly until the pH of the solution
16. stirringStir the mixture for 30 min
17. filtrationfilter off the resulting solid
18. washRinse the solid on the funnel twice with 2 L of water
19. customto air-dry for 30 min
20. customat 50° C.
21. customdry under vacuum overnight
22. customRemove the yellow color
23. customfor 30 min
24. filtrationAgain filter off the solid
25. customair-dry for 30 min
26. customvacuum dry at 40° C. overnight

ORD record

ord-62b45b8521e145ca99a4d858a75ef353

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063212B2