反应详情

4-(3-But-3-enyloxy-5-trifluoromethyl-benzoylamino)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (3.0 g) was dissolved in ethanol, and a 5 N aqueous sodium hydroxide solution (6.9 ml, 34.5 mmol) and a 30% aqueous hydrogen peroxide solution (3 ml) were added. After stirring at room temperature for two hours, DMSO (19 ml) was added to the reaction solution, and the mixture was stirred at 50° C. for four hours. The reaction solution was cooled, and then quenched with a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was sequentially washed with a saturated aqueous ammonium chloride solution, water and saturated brine, and then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 2-(3-but-3-enyloxy-5-trifluoromethyl-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-carboxylic acid tert-butyl ester (2.39 g, 67% in two steps).

1. stirringthe mixture was stirred at 50° C. for four hours
2. temperatureThe reaction solution was cooled
3. customquenched with a saturated aqueous ammonium chloride solution
4. extractionextracted with ethyl acetate
5. washThe organic layer was sequentially washed with a saturated aqueous ammonium chloride solution, water and saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe resulting residue was purified by silica gel column chromatography