反应详情

温度

80 °C

To a solution of tert-butyl (2S)-2-(4-cyanophenyl)morpholine-4-carboxylate (intermediate 17, 17.6 g, 61.1 mmol) and hydroxylamine hydrochloride (12.8 g, 183 mmol) in ethanol (120 ml) was added sodium carbonate (32.4 g, 305 mmol) in water (120 ml) at room temperature and the mixture was stirred at 80° C. for 3 hours. After removal of the solvent under reduced pressure, the residue was partitioned between water and ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was added with xylene (150 ml) and N,N-dimethylacetamide dimethylacetal (18.1 g, 122 mmol). After the solution was refluxed for 2 hours, water was azeotropically removed using a Dean-Stark water separator with molecular sieves 4A. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=3/1) to afford tert-butyl (2S)-2-(4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)-morpholine-4-carboxylate (intermediate 18, 16.9 g, 80%)

1. customAfter removal of the solvent under reduced pressure
2. customthe residue was partitioned between water and ethyl acetate
3. washThe organic layer was washed with brine
4. dry with materialdried over sodium sulfate
5. customThe solvent was evaporated under reduced pressure
6. temperatureAfter the solution was refluxed for 2 hours
7. customwater was azeotropically removed
8. concentrationThe mixture was concentrated under reduced pressure
9. customthe residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=3/1)