Synthesis
General procedure for the synthesis of 2-cyano-6-fluorophenylboronic acid from 3-fluorobenzonitrile: To a 500 mL three-necked round-bottomed flask equipped with a magnetic stirring bar, a dosing funnel, and a nitrogen inlet, under nitrogen protection, were added 3-fluorobenzonitrile (10.0 g, 82.56 mmol), triisopropyl borate (28.5 mL, 23.3 g, 123.84 mmol), and 100 mL anhydrous THF.The reaction mixture was cooled to -50 °C and a THF/hexane solution of LDA (86.7 mmol, freshly prepared from 8.77 g of diisopropylamine in 20 mL of THF and 54.2 mL of 1.6 M n-BuLi in hexane) was added dropwise over a period of 1 hour. The reaction mixture was slowly warmed to -5 °C and stirred at this temperature for 30 min. Subsequently, 70 mL of 5N HCl aqueous solution and 50 mL of MTBE were added and stirred for 30 min at room temperature. The reaction mixture was extracted with MTBE (4 x 100 mL), the organic phases were combined, washed with brine (2 x 100 mL), concentrated under reduced pressure, controlled to a temperature lower than 20 °C, and finally dried in vacuo at room temperature to give 12.16 g (89% yield) of 2-cyano-6-fluorophenylboronic acid as a white solid.LCMS m/z (M+H)+: 165.8. 1H NMR ( 300 MHz, DMSO-d6): δ 8.92 (2H), 7.65 (1H), 7.57 (1H), 7.49 (1H).
References
[1] Patent: WO2006/51410, 2006, A1. Location in patent: Page/Page column 44
[2] Journal of Organic Chemistry, 2005, vol. 70, # 15, p. 5938 - 5945
[3] Journal of Organic Chemistry, 2004, vol. 69, # 2, p. 566 - 569
