反应详情

To 5 mL of an N,N-dimethylformamide solution containing 0.19 g of 7-methoxy-4-methylquinolin-2(1H)-one, 47 mg of a 60% aqueous sodium hydride solution was added at 50° C., and the mixture was stirred at the same temperature for 40 minutes. Thereto was added dropwise 4 mL of an N,N-dimethylformamide solution containing 0.36 g of tert-butyl 4-cyano-4-(2-((methylsulfonyl)oxy)ethyl)piperidine-1-carboxylate at 50° C., and the mixture was stirred at 50 to 55° C. for 3 hours. Thereto was added 0.27 g of potassium carbonate at the same temperature, and the mixture was further stirred for 3 hours and 10 minutes. The reaction mixture was cooled to room temperature, and then water and ethyl acetate were added thereto. The organic layer was separated, washed with an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=75:25 to 50:50] to obtain 70 mg of a colorless oily substance, tert-butyl 4-cyano-4-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)piperidine-1-carboxylate.

1. additionwas added at 50° C.
2. stirringthe mixture was stirred at 50 to 55° C. for 3 hours
3. stirringthe mixture was further stirred for 3 hours and 10 minutes
4. customThe organic layer was separated
5. washwashed with an aqueous saturated sodium chloride solution
6. dry with materialdried over anhydrous magnesium sulfate
7. customthe solvent was removed under reduced pressure
8. customThe residue thus obtained
9. customwas purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=75:25 to 50:50]