反应详情

The mixture of 3-oxo-3-phenyl-propionic acid ethyl ester (5.0 g, 26 mmol), benzylamine (2.9 mL, 26 mmol) and p-toluenesulfonic acid monohydrate (0.50 g, 2.6 mmol) in toluene (100 mL) was refluxed for 3 hours and concentrated. The residual materials were dissolved in cyclopentylmethylether (150 ml) and lithium aluminum hydride (3.0 g, 78 mmol) was added portionwise at 0° C. under nitrogen atmosphere. After stirring for 3 hours, small amount of sodium sulfate saturated aqueous solution was added dropwise and stirred for one hour. The resulting mixture was filtrated to remove solid materials and concentrated. Then the resulting residue was dissolved in dichloromethane (30 mL) To the mixture was added triethylamine (1.4 mL, 10 mmol) and chloroacetylchloride (0.56 g, 7.0 mmol) at 0° C. and the resulting mixture was stirred for one hour. The reaction mixture was poured into water and extracted with chloroform. The organic extracts were dried over sodium sulfate and concentrated. The residual material was dissolved in 2-propanol (30 mL) and potassium hydroxide (1.3 g, 20 mmol) was added at room temperature. After stirring for 18 hours, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated. The residual material was purified by flash column chromatography on silica gel (hexane/ethyl acetate=100/0 to 1/1 as an eluant) to afford 4-benzyl-5-phenyl-[1,4]oxazepan-3-one (0.77 g, 2.7 mmol, 10% from ethylbenzoyl acetate) as yellow oil.

1. temperaturewas refluxed for 3 hours
2. concentrationconcentrated
3. dissolutionThe residual materials were dissolved in cyclopentylmethylether (150 ml)
4. stirringstirred for one hour
5. filtrationThe resulting mixture was filtrated
6. customto remove solid materials
7. concentrationconcentrated
8. dissolutionThen the resulting residue was dissolved in dichloromethane (30 mL) To the mixture
9. stirringthe resulting mixture was stirred for one hour
10. extractionextracted with chloroform
11. dry with materialThe organic extracts were dried over sodium sulfate
12. concentrationconcentrated
13. dissolutionThe residual material was dissolved in 2-propanol (30 mL)
14. stirringAfter stirring for 18 hours
15. extractionextracted with ethyl acetate
16. dry with materialThe organic phase was dried over anhydrous sodium sulfate
17. concentrationconcentrated
18. customThe residual material was purified by flash column chromatography on silica gel (hexane/ethyl acetate=100/0 to 1/1 as an eluant)