Synthesis
To a 250 mL round bottom flask was added 2,4-difluoroaniline (11.4 g, 4.62 mL, 45.4 mmol), dichloromethane (DCM, 103 mL) and pyridine (7.40 mL, 91 mmol). The reaction mixture was stirred at room temperature and benzyl chloroformate (8.15 mL, 54.5 mmol) was slowly added dropwise through the addition funnel. After the dropwise addition, the reaction mixture was continued to be stirred at room temperature overnight. Upon completion of the reaction, the mixture was poured into water and extracted with DCM. The organic phases were combined, washed sequentially with water and saturated saline, and then dried over anhydrous sodium sulfate. After filtration to remove the desiccant, the filtrate was concentrated under reduced pressure to afford benzyl (2,4-difluorophenyl)-carbamate (11.1 g, 42.2 mmol, 93% yield) as a white solid, which could be used for subsequent reactions without further purification.LC-MS (ESI, positive ion mode) analysis: calculated value of C14H11F2NO2 [M+H]+: 263.1; Measured value: 263.1. measured value [M+Na]+: 286.1. 1H NMR (400 MHz, DMSO-d6) δ ppm: 9.43 (br s, 1H), 7.51-7.66 (m, 1H), 7.24-7.46 (m, 6H), 7.01-7.12 (m, 1H), 5.15 (s, 2H).
References
[1] Tetrahedron Letters, 2006, vol. 47, # 36, p. 6393 - 6396
[2] Canadian Journal of Chemistry, 2009, vol. 87, # 2, p. 393 - 396
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 10, p. 2215 - 2234
[4] Tetrahedron Letters, 2008, vol. 49, # 16, p. 2607 - 2610
[5] Patent: US2008/167338, 2008, A1. Location in patent: Page/Page column 44-45
