Synthesis
Step 1: cis-4-(Aminomethyl)cyclohexyl-1-carboxylic acid (1.15 g, 7.30 mmol) was dissolved in 1,4-dioxane (12.0 mL) and 10% aqueous Na2CO3 (23.2 mL), followed by the addition of methyl 9-fluorenyl chloroformate (Fmoc-Cl, 2.26 g, 8.76 mmol). The reaction mixture was stirred at room temperature for 2.5 hours. After completion of the reaction, 1 M HCl (42.0 mL) was added to the mixture and extracted three times with ethyl acetate (EtOAc). The combined organic layers were washed sequentially with 1M HCl, water and brine. The aqueous layer was again extracted with EtOAc and all organic layers were combined and dried with anhydrous Na2SO4. The solvent was removed under reduced pressure to give the crude product. The crude product was washed with ice-cold EtOAc and dried under high vacuum to give N-Fmoc-4-aminomethylcyclohexanecarboxylic acid (2.28 g, 83% yield) as a white solid, which did not require further purification. [Ref: M. Nichifor; E. H. Schacht; Tetrahedron; 1994; 50; 12; 3747-3760].1H NMR (400 MHz, CDCl3): δ 0.87-1.02 (br.m, 2H), 1.34-1.52 (br.m, 4H), 1.81 (br. d, 2H, J = 6 Hz), 1.90-2.11 (br.s, 1H), 2.12-2.35 (br.m, 1H), 3.03 (Ψt, 2H, J = 6.2 Hz), 4.19 (br.Ψt, 1H, J = 6.5 Hz), 4.42 (br.Ψd, 2H, J = 6.5 Hz), 4.74 (br.s, 1H). 7.30 (Ψt, 2H, J = 7.4 Hz), 7.38 (Ψt, 2H, J = 7.4 Hz), 7.57 (d, 2H, J = 7.4 Hz), 7.75 (d, 2H, J = 7.4 Hz).
References
[1] Patent: EP1577289, 2005, A1. Location in patent: Page/Page column 23
[2] Organic Letters, 2008, vol. 10, # 10, p. 1881 - 1884
