trans-4-Aminocyclohexanecarboxylic acid

Uses

The trans-4-Aminocyclohexanecarboxylic acid derivative is a useful building block for the synthesis of a variety of pharmacologically active compounds such as glimepiride (L-370518).

Synthesis

The general procedure for the synthesis of 4-aminocyclohexanecarboxylic acid and cis-4-aminocyclohexanecarboxylic acid from p-aminobenzoic acid is as follows: p-aminobenzoic acid (10.0 g, 0.07 mol, 1 equiv.), 5% Ru/C catalyst (2.50 g), and 10% NaOH solution (100.0 mL) were added in an autoclave. The mixture was subjected to 100 bar hydrogen pressure and the reaction was stirred in a 15 bar hydrogen atmosphere. After 20 h of reaction, the progress of the reaction was monitored by thin layer chromatography (TLC) with DCM/MeOH/NH3 (5:5:1, v/v/v) as the unfolding agent and ninhydrin as the color developer to confirm the complete consumption of the starting material. Nuclear magnetic resonance (NMR) analysis showed that the reaction was fully converted and the ratio of cis to trans product was 1:4.6. The reaction was terminated.

References

[1] European Journal of Medicinal Chemistry, 2001, vol. 36, # 3, p. 265 - 286
[2] Biochemische Zeitschrift, 1933, vol. 262, p. 462
[3] Journal of the American Chemical Society, 1938, vol. 60, p. 2341,2343
[4] Chemische Berichte, 1942, vol. 75, p. 425,428
[5] Chemische Berichte, 1943, vol. 76, p. 1019,1023