Synthesis
3-Iodo-4-methylbenzoic acid (26.2 g, 100 mmol) and pinacol ester of bis(boronic acid) (38.1 g, 150 mmol) were used as raw materials, and 3-iodo-4-methylbenzoic acid was dissolved in DMF (300 mL) under argon protection. Subsequently, pinacol ester of bis(boronic acid), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (8.17 g, 10.0 mmol) and potassium acetate (49.0 g, 500 mmol) were added sequentially. The reaction mixture was stirred at 100 °C for 6 hours. After completion of the reaction, the mixture was acidified by adding 1 mol/L hydrochloric acid to the mixture and extracted with ethyl acetate. The organic layer was sequentially washed with brine and dried with anhydrous magnesium sulfate. Activated carbon (1 g) was added to decolorize the mixture and stirred at room temperature for 1 h. The mixture was filtered through diatomaceous earth and the filter cake was washed with ethyl acetate. The filtrate was concentrated and the resulting solid was recrystallized with isopropyl ether and filtered to afford the target product 4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzoic acid (Compound A8, 18.5 g, 71% yield). The product was characterized by 1H NMR (300 MHz, CDCl3): δ 1.36 (s, 12H), 2.61 (s, 3H), 7.26 (d, J = 8.1 Hz, 1H), 8.02 (dd, J = 8.1,1.8 Hz, 1H), 8.49 (d, J = 1.8 Hz, 1H).
References
[1] Patent: EP2269993, 2011, A1. Location in patent: Page/Page column 53
[2] Patent: WO2007/339, 2007, A1. Location in patent: Page/Page column 44-45
[3] Journal of Medicinal Chemistry, 2006, vol. 49, # 19, p. 5671 - 5686
[4] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 15, p. 4428 - 4432
[5] Patent: WO2006/104917, 2006, A2. Location in patent: Page/Page column 78-79
