Synthesis
Using trans-p-aminocyclohexanol (1.15 g, 10 mmol) and benzyl chloroformate (2.14 g, 12 mmol) as raw materials, both were co-dissolved with triethylamine (1.23 g, 12 mmol) in acetonitrile and the reaction was stirred for 1 hr at 0-5 °C. After completion of the reaction, the reaction mixture was diluted with ethyl acetate and water, the organic layer was separated and washed twice (10 mL each) with distilled water. The organic layer was dried over anhydrous sodium sulfate, 1 g of silica gel was added, and the solvent was evaporated under reduced pressure to give a dry solid. This solid was placed on top of a silica gel column and separated by column chromatography using chloroform and methanol as eluents. The eluates containing the target product (detected by TLC) were collected, combined and the solvents were evaporated under reduced pressure to give the white solid product (trans-4-hydroxycyclohexyl) benzyl carbamate in 90% yield. The melting point of the product was 161.6-163.8 °C (literature value 163-165 °C); the TLC Rf value was 0.49 (chloroform:methanol = 20:1); 1H NMR (CDCl3) δ 1.25 (m, 2H, CH2), 1.39 (m, 2H, CH2), 1.50 (d, J = 4.00 Hz, 1H, exchangeable, OH), 1.97 ( m, 4H, CH2), 3.51 (m, 1H, NCH), 3.60 (m, 1H, OCH), 4.60 (br, 1H, exchangeable, NH), 5.10 (s, 2H, CH2), 7.38 (m, 5H, ArH); HPLC purity >95%; ESI-MS m/z [M+H]+, calculated value 250.14, measured value 250.22.
References
[1] Chimia, 2005, vol. 59, # 3, p. 72 - 76
[2] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 9, p. 2437 - 2451
[3] Journal of the American Chemical Society, 2003, vol. 125, # 49, p. 15191 - 15199
[4] Chemistry - A European Journal, 2012, vol. 18, # 4, p. 1127 - 1141
[5] Patent: WO2009/131687, 2009, A2. Location in patent: Page/Page column 188
