342899-07-4

General procedure for the synthesis of (2-ethyl-4-methoxyphenyl)boronic acid from 1-bromo-2-ethyl-4-methoxybenzene: 4-bromo-3-ethylanisole (94 g, 0.437 mol) was dissolved in tetrahydrofuran (THF, 900 ml) and the solution was cooled to -78 °C. At the same temperature, n-butyllithium (249 ml, 0.55 mol) was added slowly and dropwise. Stirring of the reaction mixture was continued for 1 hour by maintaining -78°C. Subsequently, tri-n-butyl borate (177 ml, 0.655 mol) was slowly added at -78 °C. The cooling bath was removed and the reaction mixture was allowed to gradually warm up to 0°C. The reaction was quenched with 1.5N hydrochloric acid solution at 0°C. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. All organic layers were combined, washed with saturated brine and concentrated. The resulting residue was stirred in petroleum ether for 30 minutes. The solid formed was collected by filtration and dried under vacuum. A final white solid product of 65 g was obtained in 82% yield.

[1] Patent: US2006/4222, 2006, A1. Location in patent: Page/Page column 1-6
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 23, p. 7788 - 7799