[Synthesis]
4-Chlorobutanoyl chloride (57 mL, 510 mmol) was slowly added dropwise at a constant rate to a solution of anhydrous dichloromethane (520 mL) containing benzophenone hydrazone (100 g, 510 mmol) and pyridine (41 mL, 510 mmol) under nitrogen protection. Gentle reflux was maintained during the dropwise addition. The reaction mixture was continued to stir for 0.5 h and then poured into water (1 L). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product of 4-chloro-butyric acid diphenylmethylene-hydrazide. Mass spectrum (ESI+) m/z: 301.1 ([M+H]+). The crude product was dissolved in tetrahydrofuran (1.5 L) and sodium hydride (60% mineral oil suspension, 20 g, 498 mmol) was added in batches under cooling in an ice-water bath and stirred for 1 hour. Saturated aqueous ammonium chloride solution (1 L) and ethyl acetate (1 L) were added to the reaction mixture. The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product of 1-(phenylmethylimino)pyrrolidin-2-one.1H NMR (CDCl3) δ: 7.58-7.62 (m, 2H), 7.39-7.46 (m, 4H), 7.29-7.36 (m, 4H), 3.31 (t, J = 7 Hz, 2H) ), 2.32 (t, J = 7 Hz, 2H), 1.91 (quin, J = 7 Hz, 2H); mass spectrum (ESI+) m/z: 265.1 ([M+H]+). The crude product was suspended in water (3 L), concentrated hydrochloric acid (80 mL) was added and heated to reflux for 1.5 hours. The reaction was cooled to room temperature and extracted twice with dichloromethane. The aqueous phase was concentrated under reduced pressure and the residual water was subsequently removed by azeotropic distillation (three times each with anhydrous ethanol and toluene, respectively) to afford 1-aminopyrrolidin-2-one hydrochloride 56 g (81% yield) as a white solid.1H NMR (DMSO-d6) δ: 3.58 (t, J = 7 Hz, 2H), 2.33 (t, J = 7 Hz, 2H), 2.04 (quin, J = 7 Hz, 2H). J = 7 Hz, 2H); Time-of-flight mass spectrometry (ESI+) exact mass calculated value of C4H8N2O ([M+H]+): m/z = 100.0637, measured value: 100.0641. |