tert-Butyl 4-cyanobenzylcarbamate

Synthesis

(1) To a solution of 4-(aminomethyl)benzonitrile hydrochloride (5.00 g, 29.7 mmol) in dichloromethane (167 mL) at 0 °C was added sodium carbonate (7.54 g, 71.2 mmol). Subsequently, di-tert-butyl dicarbonate (7.57 mL, 32.6 mmol) was slowly added. The reaction mixture was gradually warmed to room temperature and stirred overnight. Upon completion of the reaction, water was added to terminate the reaction and the product was extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure, and the resulting crude product was purified by silica gel (NH) column chromatography (eluent: n-hexane/ethyl acetate=1:1) to give tert-butyl 4-cyanobenzylcarbamate (6.48 g, 94% yield).

References

[1] Angewandte Chemie - International Edition, 2012, vol. 51, # 18, p. 4431 - 4434
[2] Chemistry - A European Journal, 2018, vol. 24, # 68, p. 18075 - 18081
[3] Patent: WO2017/18803, 2017, A1. Location in patent: Paragraph 1552; 1553; 1554
[4] Journal of the American Chemical Society, 2012, vol. 134, # 25, p. 10317 - 10320
[5] Angewandte Chemie - International Edition, 2016, vol. 55, # 2, p. 528 - 533