Hydrochloric Acid → (4-Bromo-2,6-dimethylphenyl)boronic acid

Temperature

-75 °C

To a solution of 4-bromo-2,6-dimethyl-1-iodobenzene (150 g, 0.48 mol) in tetrahydrofuran (1500 ml) at −75° C. is added n-butyl lithium (1.6 M in hexanes, 364 ml, 0.58 mol) dropwise maintaining the temperature of the reaction mixture below −70° C. When the addition is complete the mixture is stirred at −75° C. for an additional 30 minutes and then trimethyl borate (302 g, 2.9 mol) is added dropwise. After the addition is complete the reaction is stirred at −75° C. for 1 hour, then allowed to come to room temperature and stirred for 2 hours, followed by cooling in an ice bath and acidification with 0.5 N aqueous hydrochloric acid. The mixture is extracted with ethyl acetate (3×1000 ml) and the organic extracts are combined, washed with brine, dried over anhydrous sodium sulphate. The mixture is filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-dimethylphenylboronic acid (48 g) as a white solid.

1. temperaturedropwise maintaining the temperature of the reaction mixture below −70° C
2. additionWhen the addition
3. additionAfter the addition
4. stirringis stirred at −75° C. for 1 hour
5. customto come to room temperature
6. stirringstirred for 2 hours
7. temperatureby cooling in an ice bath
8. extractionThe mixture is extracted with ethyl acetate (3×1000 ml)
9. washwashed with brine
10. dry with materialdried over anhydrous sodium sulphate
11. filtrationThe mixture is filtered
12. customthe filtrate is evaporated under reduced pressure
13. customThe residue is purified by column chromatography on silica gel

ORD record

ord-c6a1d681e830422eb8e2f8b1d14f81ac

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895761B2