反应详情

To a stirred mixture of 2-fluoromethyl-2-amino-5-benzyloxy-valeronitrile (74.8 g), triethylamine (100 g), and dry dichloromethane (450 ml), cooled in an ice bath, a solution of phthaloyldichloride (58 g) in dichloromethane (300 ml) is added slowly. Stirring is continued at room temperature overnight. The mixture is extracted with 2 N HCl (2×750 ml), washed with water (2×750 ml), dried carefully (Na2SO4), and evaporated to give a brown oil which, according to NMR analysis, contains some iso-phthalimide. The oil is dissolved in dry dichloromethane (500 ml), triethylamine (100 g) is added, and the mixture is refluxed for 3 hours. Work-up as described above gives an oil which is purified by flash-chromatography on silica (2 kg, petroleum ether/ethyl acetate 4:1). Crystallisation from ether gives the title compound (49.4 g).

1. temperaturecooled in an ice bath
2. extractionThe mixture is extracted with 2 N HCl (2×750 ml)
3. washwashed with water (2×750 ml)
4. dry with materialdried carefully (Na2SO4)
5. customevaporated
6. customto give a brown oil which
7. temperaturethe mixture is refluxed for 3 hours
8. customabove gives an oil which
9. customis purified by flash-chromatography on silica (2 kg, petroleum ether/ethyl acetate 4:1)
10. customCrystallisation from ether