Background and overview[1]
2-Benzyloxyphenylboronic acid pinacol ester is an ester compound that can be used as a pharmaceutical synthesis intermediate. If 2-benzyloxyphenylboronic acid pinacol ester is inhaled, move the patient to fresh air; if skin contact occurs, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel unwell.
Structure
Preparation method[1]
The preparation of 2-benzyloxyphenylboronic acid pinacol ester is as follows:
Step 1: Dissolve dimethylamine (5 mmol, 1.0 equiv) in Et2O (10 mL). MeOTf (6.5 mmol, 1.3 equiv) was added dropwise at 0 °C. After the addition is complete, the reaction mixture is stirred for a further 15-60 minutes at 0°C. The solution was concentrated and washed with Et2O (2 x 20 mL). The resulting compound was dried under vacuum to give the salt 2-(benzyloxy)-N,N,N-trimethylaniline triflate (2g): a white solid (1.8g, 92%). 1HNMR (MHz, D6-DMSO) δ7.80 (dd, J=8.5, 1.2Hz, 1H), 7.59 (ddd, J=8.3, 7.6, 2.9Hz, 3H), 7.53-7.37 (m, 4H), 7.18 (ddd, J=8.6, 7.5, 1.4Hz, 1H), 5.38 (s, 2H), 3.64 (s, 9H); 13C{1H}NMR (101MHz, D6-DMSO) δ150.6, 135.5, 133.5, 131.9 , 128.8, 128.6, 128.4, 121.9, 121.4, 115.8, 71.0, 55.1; HRMSm/z (ESI) calculated value C16H20NO (M-OTf) + 242.1539, measured value 242.1541.
Step 2: Add 4-methoxy-N,N,N-trimethylaniline trifluoromethanesulfonate 1a (63.6mg, 0.2mmol), bis-(pinacol) to a 25mL Schlenk tube ) Diboron (127.0 mg, 0.5 mmol), Ni(COD)2 (3.3 mg under argon, 6 mol%), ICy·HCl (6.5 mg, 12 mol%), KOtBu (44.9 mg, 200 mol%), toluene (0.5mL) and 2-ethoxyethanol (0.5mL). The resulting mixture was stirred at 50°C for 24 hours under Ar, monitored by TLC. The solution was then cooled to room temperature and the solvent was removed directly under vacuum. The crude product 2-benzyloxyphenylboronic acid pinacol ester was purified by silica gel column chromatography (ethyl acetate/petroleum ether = 1:100): white solid (34.3 mg, 55%).
1HNMR (MHz, CDCl3) δ7.72 (dd, J=7.3, 1.7Hz, 1H), 7.63 (d, J=7.3Hz, 2H), 7.44-7.35 (m, 3H), 7.31 (d, J=7.2Hz, 1H), 7.04-6.91 (m, 2H), 5.14 (s, 2H), 1.38 (s, 12H); 13C{1H}NMR (101MHz, CDCl3) δ163.2, 137.6, 136.7, 132.5 , 128.1, 127.3, 126.7, 120.6, 112.0, 83.4, 69.9, 24.9; ATR-FTIR (cm-1) 2977, 2925, 2888, 2853, 1598, 1443, 1355, 1320, 1141, 1072, 861, 761, 744 , 656; HRMSm/z (ESI) calculated value C19H24BO3 (M+H) + 311.1813, measured value 311.1821.
Main reference materials
[1] Nickel-CatalyzedBorylationofAryl-andBenzyltrimethylammoniumSaltsviaC-NBondCleavage
