General procedure for the synthesis of (trans-4-aminocyclohexyl)methanol from ethyl trans-4-aminocyclohexanecarboxylate:
1. a suspension was prepared by suspending ethyl trans-4-aminocyclohexanecarboxylate (Intermediate 16; 7.2 g, 0.034 mol) in THF (200 mL).
2. the above suspension was slowly added to lithium aluminum hydride (69 mL of 1 M THF solution, 0.069 mol) and the reaction system was kept at 0 °C.
3. The reaction mixture was stirred continuously for 1 hour at 0 °C.
4. The ice bath was removed and the reaction mixture was stirred overnight at room temperature.
5. The stirred reaction mixture was placed back in the ice bath to cool and water (6.9 mL), 15% NaOH solution (21 mL) and water (21 mL) were added slowly and carefully in sequence.
6. After continued stirring at room temperature for 30 min, the reaction mixture was filtered through a thin layer of diatomaceous earth (1 cm) and the filter cake was washed with THF.
7. The filtrate was combined with the washings and subjected to evaporation and concentration to afford a white solid product, the title compound (trans-4-aminocyclohexyl) methanol (4.4 g, 99% yield).
Product characterization data: 1H NMR (300 MHz, DMSO) δ 3.18 (d, J = 6.3 Hz, 2H), 2.42 (m, 1H), 1.79-1.60 (m, 4H), 1.30-1.13 (m, 1H), 1.05-0.72 (m, 4H).
