4-(2-Tetrahydropyranyloxy)phenylboronic acid

36603-49-3

150-46-9

7732-18-5

182281-01-2

The general procedure for the synthesis of 4-(2'-tetrahydrophenoxy)phenylboronic acid from 2-(4-bromophenoxy)tetrahydro-2H-pyran, triethyl borate, and water (electrophoretic grade) was as follows: tetrahydrofuran (THF, 10 mL) was added to a reaction flask containing magnesium powder (24.3 g, 97.2 mmol) and a small amount of iodine crystals and stirred at room temperature for 1 minutes. Subsequently, a THF solution (40.0 mL) of 2-(4-bromophenoxy)tetrahydro-2H-pyran (25.0 g, 97.2 mmol) was slowly added and stirred for 5 min at room temperature under nitrogen protection, then refluxed for 2 hours. After the reaction was completed, it was cooled to room temperature to obtain the Grignard reagent solution. In another four-necked flask, triethyl borate (31.3 g, 292 mmol) and THF (600 mL) were added and cooled to -15 °C after nitrogen displacement. The Grignard reagent solution was cooled to 0 °C and slowly added dropwise to the THF solution of triethyl borate through a cannula over 30 min. After the dropwise addition was completed, the reaction was continued at 0 °C for 1 h. Gray solid precipitation was observed. 10% aqueous ammonium chloride solution (150 mL) was added to the reaction mixture and stirred at room temperature for 16 hours. The organic layer was extracted by adding ethyl acetate (200 mL), washed sequentially with water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration to remove the desiccant, the solvent was removed by distillation under reduced pressure to give a pink solid. Recrystallization with a solvent mixture of ethyl acetate and hexane (1:10, v/v) afforded 4-(tetrahydro-2H-pyran-2-yloxy)phenylboronic acid (18.3 g, 83% yield) as a white solid.