Triisopropyl borate → 1-Benzothien-7-ylboronic acid

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 (min) 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. Slurry the dried solid with 2 L of n-heptane for 30 min to remove the yellow color. Again, filter the solid, air-dry for 30 min, and then 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, 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. washWash the aqueous layer with additional methyl-tert-butyl ether (4 L)
13. customAgain, separate the aqueous layer and transfer to a 12-L, 3-neck round bottom flask
14. customfitted with a mechanical stirrer
15. temperatureCool the solution to +5° C. with an ice-water bath
16. additionAdd concentrated HCl slowly until the pH of the solution
17. stirringStir the mixture for 30 minutes (min)
18. filtrationfilter off the resulting solid
19. washRinse the solid on the funnel twice with 2 L of water
20. customto air-dry for 30 min
21. customat 50° C.
22. customdry under vacuum overnight
23. customfor 30 min
24. customto remove the yellow color
25. filtrationAgain, filter the solid
26. customair-dry for 30 min
27. customvacuum-dry at 40° C. overnight

ORD-Eintrag

ord-06720b0a9ca9443fa7c6b064707adf4b

Quelldatensatz

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08114872B2