Water → racemic 8-cyclohexyl-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

Participants

Reaction Conditions

Reaction Steps

A solution of 5-chloro-2-cyclohexyl-valeric acid hydrazide hydrochloride (144 mg) and TEA (0.32 ml) in ethanol (1 ml) was added to a solution of ethyl (E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylimidate dihydrochloride obtained in Example 1 (167 mg) and TEA (0.32 ml) in ethanol (1.6 ml), and the reaction solution was stirred at 70° C. for two days. The reaction solution was left to cool to room temperature. Then, ethyl acetate and water were added to the reaction solution, and the organic layer was separated. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: heptane-ethyl acetate system) and again purified by silica gel column chromatography (elution solvent: ethyl acetate-methanol system) to obtain 27 mg of racemic 8-cyclohexyl-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine. Then, the racemate was separated by CHIRALPAK™ IB manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: 20% ethanol-hexane) to obtain the title optically active compound with a retention time of 16 minutes and positive optical rotation (11.0 mg; 100% ee) and the title optically active compound with a retention time of 39 minutes and negative optical rotation (10.2 mg; 100% ee).

Provenance & Evidence