反应详情

To a stirred solution of 2-fluoromethyl-2-amino-5-benzyloxypentanenitrile (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 2N HCl (2×750 ml), washed with water (2×750 ml), dried carefully (Na2SO4), 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). Crystallization from ether gives 2-fluoromethyl-2-phthalimido-5-benzyloxypentanenitrile (49.4 g).

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