Background and overview of the preparation method of 4-bromomethylphenylboronic acid pinacol ester
4-Bromomethylphenylboronic acid pinacol ester is an organic intermediate that can be widely used in Suzuki coupling reactions.
Preparation method of 4-bromomethylphenylboronic acid pinacol ester
Preparation method report 1 of 4-bromomethylphenylboronic acid pinacol ester,
Add p-bromobenzaldehyde (500 mg, 2.70 mmol), MeOH (5 mL), AcOH (773 μL, 13.5 mmol) and NaBH3CN (339 mg, 5.41 mmol) to a round-bottomed flask at room temperature, and stir the resulting solution for 15 minute. When TLC indicated the reaction was complete, the reaction was quenched with water (5 mL). The resulting mixture was diluted with ethyl acetate (15 mL) and washed with brine (1 x 5 mL). The aqueous layer was further extracted with ethyl acetate (3×5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography to afford purified product 41 (479 mg, 95%) as a colorless oil.
Analytical TLC (silica gel 60), 50% ethyl acetate in n-hexane, Rf=0.5; 1HNMR (300MHz, CDCl3) δ7.39(d,J=8.4Hz,2H),7.08(d,J =8.3Hz, 2H), 4.45 (s, 2H), 3.55 (s, 1H); 13CNMR (75MHz, CDCl3) δ 139.5, 131.4, 128.4, 121.2, 63. Boric acid pinacol ester 9; LRMS (EI) 188.0 ( [M]+,52),186.0(13),107.1(77),79(100),77.0(86). Characterization data are consistent with reported data (Org Lett, 2007, 9, 5429).
Add alcohol 41 (250 mg, 1.34 mmol), bis(pinacol) diboron (512 mg, 2.02 mmol), KOAc (395 mg, 4. propyl carbonate 03 mmol), Pd(dppf)Cl2 (98.0 mg, 0.134 mmol) and degassed dioxane (4 mL). The resulting solution was stirred for 16 hours. When TLC indicated the reaction was complete, the reaction mixture was diluted with ethyl acetate (15 mL) and filtered through silica gel. The organic portion was washed with water (5 mL) and then brine (1 x 5 mL). The aqueous layer was further extracted with ethyl acetate (3×5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography to afford purified product 42 (303 mg, 96%) as a colorless oil. Analytical TLC (silica gel 60), 50% ethyl acetate in n-hexane, Rf=0.5; 1HNMR (MHz, CDCl3) δ7.75 (d,J=7.9Hz, 2H), 7.28 (d,J=7.8Hz ,2H),4.59(s,2H),3.36(s,1H),1.31(s,12H); 13CNMR(100MHz,CDCl3)δ144.1,134.8,125.9,83.7,64.6,24.7; LRMS(EI)234.1([ M]+,33),219.1(44),148.1(48),135.0(100); the calculated HRMS(EI) value of C13H19BO3([M]+) is 234.1422, and the measured value is 234.1424. Due to quadrupole broadening, no 13CNMR signal corresponding to carbon directly attached to the boron atom was reported.
Preparation method report 2 of 4-bromomethylphenylboronic acid pinacol ester,
Add anhydrous magnesium sulfate (40.02g, 300.0mmol), p-tolueneboric acid (13.60g, 100.0mmol), and pinacol (11.81g, 100.0mmol) into anhydrous ether (200mL), and stir at room temperature for 14 -16 hours, filtered, and rotary evaporated to remove the solvent. Use petroleum ether as the eluent to pass through the column to separate and obtain pinacol p-tolueneborate (20.90 g, yield 95.8%).
Pinacol p-tolueneborate (10.91g, 50.0mmol), bromosuccinimide (NBS, 9.91g, 55.0mmol), azobisisobutyronitrile (AIBN, 0.44g, 2.0mmol) Dissolve in dry carbon tetrachloride (CCl4, 200mL), stir under reflux for 14 hours, filter, evaporate to remove the solvent, dissolve in ethyl acetate (200mL), and wash with distilled water (100mL) and saturated sodium chloride aqueous solution (100mL) Once, dry with anhydrous sodium sulfate, rotary evaporate, and finally use petroleum ether as the eluent to pass through the column to separate and obtain 4-bromomethylphenylboronic acid pinacol ester (11.30g, yield 76.1%).
References
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