Synthesis
General procedure for the synthesis of ethyl trans-4-aminocyclohexanecarboxylate from ethanol and trans-4-aminocyclohexanecarboxylic acid hydrochloride:
1. concentrated hydrochloric acid (7 mL) was added to a suspension of (1r,4r)-4-aminocyclohexanecarboxylic acid hydrochloride (6.32 g, 0.035 mol) in ethanol (100 mL) and the mixture was stirred.
2. The mixture was heated to 60 °C and the reaction was kept overnight.
3. Upon completion of the reaction, the mixture was evaporated under vacuum to remove the solvent.
4. The residue was thoroughly removed from water by azeotropy with water, followed by azeotropy with ethanol and finally azeotropy with toluene to afford the title product ethyl trans-4-aminocyclohexanecarboxylate as a white solid (7.2 g, 98% yield). 5. The structure of the product was determined by 1H2O2 analysis.
5. The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ 4.05 (q, J = 7.1 Hz, 2H), 2.95 (bs, 1H), 2.30-2.15 (m, 1H), 2.02-1.88 (m, 4H), 1.43-1.28 (m, 4H), 1.22-1.13 (t, J = 6.9 Hz, 3H). Hz, 3H).
References
[1] Patent: WO2016/46390, 2016, A1. Location in patent: Page/Page column 44
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 22, p. 9199 - 9221
