4-Benzyloxy-3-methylbenzeneboronic acid

338454-32-3

338454-30-1

General procedure for the synthesis of 4-benzyloxy-3-methylbenzeneboronic acid from 2-benzyloxy-5-bromotoluene: 4-bromo-1-benzyloxy-2-methylbenzene (6.9 g, 25 mmol) was dissolved in molecularly sieve-dried tetrahydrofuran (37.5 mL) and the solution was cooled to -78 °C. A n-hexane solution of 1.6 M n-butyllithium (17 mL, 27.5 mmol) was added slowly and dropwise over a period of 30 min, keeping the reaction temperature from exceeding -70 °C. After continued stirring at this temperature for 10 min, trimethyl borate (8.3 mL, 75 mmol) was added dropwise over 25 min below -70 °C. The reaction mixture was allowed to warm slowly to room temperature and stirred overnight. The reaction mixture was then cooled to 0 °C and aqueous 1 N hydrochloric acid was added dropwise. The reaction mixture was diluted with water and ethyl acetate to separate the organic and aqueous phases, and the aqueous phase was then extracted with ethyl acetate. The organic phases were combined, washed sequentially with water and saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated. 4-Benzyloxy-3-methylphenylboronic acid 3.95 g (yield 65%) was obtained as a white powder. Mass spectrum (ISN): 301.2 (M-H)-.