867333-43-5

121-43-7

42872-74-2

867333-43-5

Step 1: Synthesis of 5-cyano-2-methylphenylboronic acid First, 9.5 g (50 mmol) of 3-bromo-4-methylbenzonitrile was placed in a 500 mL three-necked flask and the atmosphere inside the flask was replaced with nitrogen. Then, 250 mL of tetrahydrofuran (THF) was added and the mixture was stirred at -78 °C for 30 min. Slowly 34 mL (55 mmol) of 1.63 M hexane solution of n-butyllithium (n-BuLi) was added dropwise to the above mixture and the reaction was maintained at -78 °C for 1.5 hours. Subsequently, 7.3 mL (65 mmol) of trimethyl borate was added to the reaction system, and the reaction solution was slowly warmed to room temperature and stirred for 20 hours. Upon completion of the reaction, 100 mL of 1 M hydrochloric acid was added to the system and stirred for 30 minutes. The reaction mixture was transferred to a partition funnel and the aqueous and organic layers were separated. The aqueous layer was extracted with ethyl acetate, the organic phase and extract were combined and washed with saturated sodium chloride solution. Anhydrous magnesium sulfate was added to the washed organic phase to dry. After drying, gravity filtration was performed and the filtrate was concentrated to obtain the crude product. The crude product was washed with toluene and hexane to give 4.3 g of white solid in 53% yield. The resulting white solid was confirmed to be 5-cyano-2-methylphenylboronic acid by nuclear magnetic resonance (NMR) spectral analysis. The synthesis scheme of step 1 is shown below (a-10).