Benzenepropanoic acid, b-(nitromethyl)-, methyl ester → 4-Phenyl-2-pyrrolidinone

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Reaction Steps

A solution of 4-nitro-3-phenyl-butyric acid methyl ester (4.02 g, 18 mmol) and Raney-Nickel (6 ml, slurry in water) in methanol (30 ml) was stirred under hydrogen atmosphere for 3 hours. After filtration using celite and removal of the solvent under reduced pressure, residue was partitioned between water and ethyl acetate. The organic layer was washed with water and brine, and then dried over sodium sulfate. The solvents were removed under reduced pressure, and the residue was dissolved in toluene (50 ml) and the resulting solution was refluxed for 6 hours. Removal of the solvent afforded crude 4-phenyl-pyrrolidin-2-one. A solution of crude 4-phenyl-pyrrolidin-2-one in tetrahydrofuran (20 ml) was added to a solution of lithium aluminum hydride (1.34 g, 35.3 mmol) and the mixture was refluxed for 6 hours. After quenching the reaction with 20% aqueous sodium hydroxide, a solution of di-tert-butyl dicarbonate (4.14 g, 19 mmol) was added and the mixture was stirred for 3 hours. Aqueous citric acid and aqueous potassium hydrogen sulfate was added to acidify the solution, and the solution was extracted with toluene. The organic layer was washed with water, aqueous sodium bicarbonate, brine, and dried over sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified with silica gel column chromatography (eluent; hexane/ethyl acetate=9/1) to afford 1-tertbutoxycarbonyl-3-phenyl-pyrrolidine (1.84 g, 42%).

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