4-Bromo-2-chlorophenol → 3-Chloro-4-hydroxyphenylboronic Acid

Temperature

-78 °C

A dry 250 ml r.b. flask was loaded with 4-bromo-2-chlorophenol (5.00 g, 24.1 mmol) and purged with N2(g). Anhydrous THF (100 mL) added with stirring and the vessel cooled to −78° C. (dry ice/acetone bath). After 30 mins n-BuLi, 2.3 M in hexanes, (12.9 mL, 28.9 mmol) was added dropwise over 20 min. The reaction was left to stir for 1 h. Triisopropyl borate (6.65 mL, 28.9 mmol) was added dropwise with the reaction still at −78° C. After 15 min of stirring at this temperature the dry ice/acetone bath was removed. At about 0° C. 2 M HCl(aq) (5 mL) was added and the reaction left to stir for a further 15 min. THF removed under vacuum and residues taken up in ethyl acetate (50 mL). Distilled H2O (50 mL) was added and the organic layer separated. The aqueous layer was extracted with ethyl acetate (50 mL×2). The organic portions were combined and washed with sat. Na2CO3 (aq). The aqueous layer was separated and treated with 2M HCl (aq) until the pH was about 4. This was then extracted with ethyl acetate (50 mL×2). The organic portions were then dried over MgSO4 and solvent removed. The resultant brown residues were taken up in a minimum of ethyl acetate (2-3 mL) and added to dropwise to hexane (50 mL) with stirring. The brown ppt was filtered to give the title compound as a brown solid (1.11 g, 27%).

1. custompurged with N2(g)
2. additionAnhydrous THF (100 mL) added
3. waitThe reaction was left
4. stirringto stir for 1 h
5. customwas removed
6. customAt about 0° C
7. addition2 M HCl(aq) (5 mL) was added
8. waitthe reaction left
9. stirringto stir for a further 15 min
10. customTHF removed under vacuum and residues
11. additionDistilled H2O (50 mL) was added
12. customthe organic layer separated
13. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×2)
14. washwashed with sat. Na2CO3 (aq)
15. customThe aqueous layer was separated
16. additiontreated with 2M HCl (aq) until the pH was about 4
17. extractionThis was then extracted with ethyl acetate (50 mL×2)
18. dry with materialThe organic portions were then dried over MgSO4 and solvent
19. customremoved
20. additionadded to dropwise to hexane (50 mL)
21. stirringwith stirring
22. filtrationThe brown ppt was filtered

ORD record

ord-fb93d8fe0dbe4cf58b825fdda308b149

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022224B2