Synthesis
The general procedure for the synthesis of 4-cyanomethylcarbamoylphenylboronic acid from 4-carboxyphenylboronic acid and aminoacetonitrile hydrochloride was as follows: oxalyl chloride (5.9 mL, 66 mmol) was added dropwise to a suspension of 4-carboxyphenylboronic acid (5.0 g, 30 mmol) in DMF (5 mL) and dichloromethane (200 mL) at 0 °C. After the rate of gas release slowed down, the ice bath was removed and the reaction system was allowed to warm up to room temperature naturally within 30 min. Subsequently, the reaction mixture was heated at 40 °C for 3 h until all solids were completely dissolved. Dichloromethane was removed by distillation and the remaining DMF solution was cooled to 0 °C. At this temperature, a DMF (80 mL) solution of aminoacetonitrile hydrochloride (3.05 g, 33 mmol) and a solution of DIPEA (13 mL, 75 mmol) were slowly added dropwise. After completion of the dropwise addition, the ice bath was removed and the reaction mixture was stirred continuously for 16 hours at room temperature. Upon completion of the reaction, most of the DMF was evaporated under reduced pressure and the residue was subjected to liquid-liquid partitioning with ethyl acetate and 2 M aqueous hydrochloric acid. The aqueous phase was extracted twice more with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 4-cyanomethylcarbamoylphenylboronic acid as a light yellow waxy solid (5.34 g, 87% yield). The product was characterized by 1HNMR (J6-DMSO, 300 MHz): δ 9.18 (1H, br, t, J=5.1 Hz), 7.8-7.9 (4H, m), 4.31 (2H, d, J=5.4 Hz).The LC-MS analysis showed the following results: retention time 0.9 min; mass-to-charge ratio m/z 203.3 [M-H]-.
References
[1] Patent: WO2009/29998, 2009, A1. Location in patent: Page/Page column 52-53
[2] Patent: WO2008/109943, 2008, A1. Location in patent: Page/Page column 60
