Citric Acid → HCID 78324915, compound

Participants

Reaction Conditions

Reaction Steps

Pyrrolidine (0.03 ml, 0.36 mmol) was added to a suspension of the tert-butyl 6-(3-formyl-4-methoxy-2-methylphenyl)-3-methylpyridine-2-carboxylate produced in Example 10-2 (1.31 g) and 5,5-dimethylcyclohexane-1,3-dione (1.17 g, 8.33 mmol) in ethanol (26.2 ml) at room temperature, and the mixture thus obtained was then stirred at 80° C. for 3 hours. After air-cooling, the solvent was distilled away from the reaction solution under reduced pressure. The residue thus obtained was dissolved in chloroform (26.2 ml), and p-toluenesulfonic acid monohydrate (0.19 g, 1.09 mmol) was then added to the solution obtained above at room temperature. The mixture thus obtained was stirred at 70° C. for 2.5 hours. After air-cooling, water was added to the reaction solution, and the mixed solution was then extracted with dichloromethane twice. The organic layer thus obtained was dried over anhydrous sodium sulfate, and the solvent was then distilled away under reduced pressure. The residue thus obtained was dissolved in dichloromethane (51 ml), and trifluoroacetic acid (25.5 ml) was then added to the solution obtained above at room temperature. The mixture thus obtained was stirred at the same temperature as above for 4.5 hours. Thereafter, the solvent was distilled away from the reaction solution under reduced pressure. A small amount of saturated aqueous solution of sodium hydrogen carbonate was added to the residue thus obtained, and thereafter, a 10% aqueous solution of citric acid was added thereto. The solution thus mixed was extracted with dichloromethane. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then dissolved in THF (51 ml). A 1 N aqueous solution of sodium hydroxide (7.96 ml) was added to the solution obtained above, and the mixture thus obtained was then stirred at room temperature. Thereafter, water was added to the reaction solution, and the mixed solution was then washed with diethyl ether. A 1 N aqueous solution of hydrochloric acid (7.96 ml) was added to the water layer thus obtained, and the mixed solution was then extracted with dichloromethane. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the solid thus obtained was then washed with a mixed solution of diethyl ether and hexane, followed by collection by filtration and drying, to obtain the title compound (0.966 g, yield: 50%).

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