trans-1,2-cyclohexanedicarboxylic acid was prepared from phthalic anhydride via catalytic hydrogenation, resolution, and acidification. The resulting product had an optical purity (ee value) of 99.8% and a total yield of 40%, meeting both quality and industrialization requirements. The reaction formula is as follows:
Figure: Synthetic route diagram of trans-1,2-cyclohexanedicarboxylic acid
trans-1,2-Cyclohexanedicarboxylic Acid is used as a reagent in the synthesis of enantiopure (α-cyanoalkyl)(tetrahydropyrido[4,3-b]indolecarbonyl)cyclohexanecarboxamides and its analogs as selective cathepsin K inhibitors for the treatment of osteoarthritis. Also used as a reagent in the synthesis of novel cyclopentanedicarboxamide sodium channel blockers as a potential treatment for chronic pain.
It is purified by recrystallisation from EtOH or H2O. It is formed by hydrolyzing the anhydride with water. The dimethyl ester has m 95-96o (from *C6H6/pet ether). [Abell J Org Chem 22 769 1957, Smith & Byrne J Am Chem Soc 72 4406 1950, Linstead et al. J Am Chem Soc 64 2093 1942, Beilstein 9 III 3812, 9 IV 2801.] The 1R,2R-(-)-trans-cyclohexane-1,2-acid [46022-05-3] has m 171-182o and [ ] D -20o (c 1, Me2CO). cis-Cyclohexane-1,2-dicarboxylic anhydride (cis-hexahydrophthalic anhydride) [85-42-7, 13149-00-3] M 154.2, m 32-34o, b 158o/17mm. It has been obtained by heating the trans-acid or anhydride at 200o. Crystallise it from *C6H6/Et2O or distil it. [Kohler & Jansen J Am Chem Soc 60 2145 1938, Abell J Org Chem 22 769 1957, Beilstein 17 II 452, 17 III/IV 5931.]
