反应详情

IPEA (0.5 mL), EDC (128 mg) and HOBT (90.4 mg) were added to a solution of 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (100 mg) and 1-o-tolylethylamine (60 mg) in DMF (5 mL), and the reaction solution was stirred at room temperature for 1 hour. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system→ethyl acetate-methanol system) to obtain 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-o-tolylethyl)amide. Sodium hydride (containing mineral oil at 40%, 50 mg) was added to a solution of the resulting 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-o-tolylethyl)amide in DMF (4 mL), and the reaction solution was stirred at room temperature for 10 minutes. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system→ethyl acetate-methanol system) to obtain 60 mg of the title compound as a racemate. The compound (10 mg) was fractionated using CHIRALPAK™ AD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase: hexane:ethanol=7:3) to obtain the title optically active substance with a retention time of 39 minutes (4.4 mg; >99% ee) and the title optically active substance with a retention time of 48 minutes (4.4 mg; >99% ee). The physical properties of the compounds are as follows.

1. customthe organic layer was partitioned
2. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
3. customthe solvent was evaporated under reduced pressure
4. customThe residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system→ethyl acetate-methanol system)