The general procedure for the synthesis of 3-hydroxymethylphenylboronic acid from triisopropyl borate and ((3-bromobenzyl)oxy)(tert-butyl)dimethylsilane is as follows:
Example 3B: Synthesis of 3-(hydroxymethyl)phenylboronic acid
Example 3A (150 mg, 0.498 mmol) was dissolved in THF (2.49 mL) and the solution was cooled to -78 °C. Under stirring, n-butyllithium (431.1 μL, 0.647 mmol) was slowly added and stirred continuously for 30 hours at this temperature. Subsequently, triisopropyl borate (231 μL, 0.996 mmol) was added and stirring was continued for 20 minutes. After that, the reaction mixture was slowly warmed up to room temperature and stirring was continued for 2.5 hours. After completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed sequentially with water and brine, then dried with anhydrous sodium sulfate, filtered, and concentrated under vacuum. The resulting crude product was dissolved in HPLC solvent B (90:10:0.1 MeCN:H2O:TFA) and stirred at room temperature for 1 hour. Afterwards, the solution was concentrated in vacuum and purified by preparative liquid chromatography (using an Axia Luna 5μ C18 30×100 mm column with a 10-minute gradient, 20 to 100% B, A = 10:90:0.1 MeCN:H2O:TFA, B = 90:10:0.1 MeCN:H2O:TFA) to give Example 3B (57 mg, yield 75%).
1H NMR (400 MHz, ACETONITRILE-d3) δ ppm: 7.75 (1H, s), 7.67 (1H, d, J = 7.28 Hz), 7.40-7.48 (1H, m), 7.30-7.40 (1H, m), 4.60 (2H, s).
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