反应详情

温度

-50 °C

In THF (10 ml) was dissolved ethyl 7-morpholino-5-oxo-2,3,4,5-tetrahydro-1-benzoxepine-4-carboxylate (924 mg, 2.89 mmol), and to the mixture was added at −30° C. a solution of sodium boro hydride (164 mg, 4.34 mmol) in methanol (3 ml). The mixture was stirred at −20° C. to −15° C. for 30 minutes, and the mixture was cooled to −50° C., to which was added water (15 ml). The mixture was extracted with ethyl acetate (15 ml×3), and the organic layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in THF (10 ml), and to the mixture were added at 0° C. triethylamine (2.02 ml, 14.5 mmol) and methanesulfonylchloride (0.336 ml, 4.34 mmol). The mixture was stirred at room temperature for 17 hours and concentrated under reduced pressure. To the residue was added water (15 ml), and the mixture was extracted with ethyl acetate (20 ml×3). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified with column chromatography (silica gel 30 g, ethyl acetate/hexane=1/5), and the desired fraction was concentrated under reduced pressure to give ethyl 7-morpholino-2,3-dihydro-1-benzoxepine-4-carboxylate (691 mg, 2.28 mmol, 79%).

1. extractionThe mixture was extracted with ethyl acetate (15 ml×3)
2. dry with materialthe organic layer was dried with anhydrous magnesium sulfate
3. concentrationconcentrated under reduced pressure
4. dissolutionThe residue was dissolved in THF (10 ml)
5. stirringThe mixture was stirred at room temperature for 17 hours
6. concentrationconcentrated under reduced pressure
7. additionTo the residue was added water (15 ml)
8. extractionthe mixture was extracted with ethyl acetate (20 ml×3)
9. dry with materialThe organic layer was dried with anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified with column chromatography (silica gel 30 g, ethyl acetate/hexane=1/5)
12. concentrationthe desired fraction was concentrated under reduced pressure