Phthaloyl chloride → 2-Fluoromethyl-2-phthalimido-5-benzyloxypentanenitrile

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Reaction Steps

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).

Provenance & Evidence