反应详情

In THF (15 ml) was dissolved diusopropylamine (1.018 ml), and to the mixture was added dropwise at 0° C. n-butyl lithium (4.2 ml). The mixture was stirred at the same temperature for 30 minutes. To the mixture was added dropwise a solution of ethyl 4-(2-methoxycarbonyl-4-morpholinophenoxy)butyrate (1829 mg, 5.18 mmol) in THF (5 ml) at −78° C., ice bath was removed, and the mixture was stirred for 7 hours. To the mixture was added at 0° C. 10% ammonium chloride solution (30 ml), and the mixture was extracted with ethyl acetate (30 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 50 g, ethyl acetate/hexane=1/5), and the desired fraction was concentrated under reduced pressure to give ethyl 7-morpholino-5-oxo-2,3,4,5-tetrahydro-1-benzoxepine-4-carboxylate (924 mg, 2.89 mmol, 5.6%).

1. customice bath was removed
2. stirringthe mixture was stirred for 7 hours
3. additionTo the mixture was added at 0° C
4. extraction10% ammonium chloride solution (30 ml), and the mixture was extracted with ethyl acetate (30 ml×3)
5. dry with materialThe organic layer was dried with anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified with column chromatography (silica gel 50 g, ethyl acetate/hexane=1/5)
8. concentrationthe desired fraction was concentrated under reduced pressure