反应详情

Under a nitrogen atmosphere, a 21% wt. sodium ethoxide-ethanol solution (1.23 ml, 3.31 mmol) was added to toluene (100 ml) at room temperature, and the resulting mixture was refluxed by the use of a Dean-Stark trap. A solution of ethyl 5-[benzyl(2-ethoxy-2-oxoethyl)amino]pentanoate (965.9 mg, 3.01 mmol) in toluene (50 ml) was added dropwise thereto over a period of 1.5 hours. After 3 hours, a 21% wt. sodium ethoxide-ethanol solution (1.23 ml, 3.31 mmol) was further added thereto. After another 1 hour, the toluene (30 ml) was distilled off with heating. After 5 hours, the reaction solution was poured into water (200 ml) and extracted with ethyl acetate (100 ml×2), and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain ethyl 1-benzyl-3-oxoazepane-4-carboxylate (158.5 mg, 19%) and ethyl 1-benzyl-3-oxoazepane-2-carboxylate (213.8 mg, content=about 75%).

1. temperaturethe resulting mixture was refluxed by the use of a Dean-Stark trap
2. waitAfter 3 hours
3. waitAfter another 1 hour
4. distillationthe toluene (30 ml) was distilled off
5. temperaturewith heating
6. waitAfter 5 hours
7. additionthe reaction solution was poured into water (200 ml)
8. extractionextracted with ethyl acetate (100 ml×2)
9. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
10. customThe organic layer dried
11. concentrationwas concentrated under reduced pressure
12. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)