[2,6-Dimethyl-4-(phenylmethoxy)phenyl]boronic acid

Synthesis

The general procedure for the synthesis of 2,6-dimethyl-4-benzyloxyphenylboronic acid from (4-bromo-3,5-dimethyl)phenylbenzyl ether was as follows: 5-(benzyloxy)-2-bromo-1,3-dimethylbenzene (12a, 2.91 g, 10 mmol, prepared by the method disclosed in the patent application) was dissolved in a dry ice bath in 35 mL of anhydrous tetrahydrofuran, followed by a slow addition of n butyl lithium (4.8 mL, 12 mmol). The reaction mixture was stirred in a dry ice bath for 1.5 h. Tripropyl borate (5.64 g, 30 mmol) was added, and then the reaction system was gradually warmed to 30 °C and stirred continuously for 12 h. The reaction mixture was then stirred in a dry ice bath for 1.5 h. Upon completion of the reaction, 10 mL of 2M hydrochloric acid was slowly added dropwise to the reaction solution, followed by cooling the mixture to room temperature and continued stirring for 2 hours. The resulting mixture was concentrated under reduced pressure and the solid was collected by filtration. The solid was washed sequentially with 10 mL of water and 10 mL of hexane to afford 2,6-dimethyl-4-benzyloxyphenylboronic acid (4-(benzyloxy)-2,6-dimethylphenylboronic acid, 12b, 1.54 g, 60.2% yield) as a white solid. Mass spectrum (ESI) m/z: 257.2 [M + 1].

References

[1] Patent: EP2803664, 2014, A1. Location in patent: Paragraph 0158; 0159
[2] Patent: EP1726580, 2006, A1. Location in patent: Page/Page column 117
[3] Patent: WO2013/144098, 2013, A1. Location in patent: Page/Page column 140