[Synthesis]
Hydroxylamine hydrochloride (1.55 g, 22.3 mmol) was dissolved in water (3.41 mL) under stirring conditions at room temperature, followed by the slow addition of aqueous 8 N sodium hydroxide (3.35 mL, 26.8 mmol). The reaction system was warmed up to 45 °C and a methanol (5.50 mL) solution of 3,3-dimethoxyacrylonitrile (2.27 g, 20.1 mmol) was added dropwise at this temperature for 30 min. After the dropwise addition, the reaction was kept at 45 °C with continued stirring for 1 hour. After confirming the complete consumption of 3,3-dimethoxyacrylonitrile by TLC monitoring, 8 N aqueous sodium hydroxide solution (1.25 mL, 10.1 mmol) was added to the reaction system and the temperature was raised to 60 °C and the reaction continued to be stirred for 6 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure at 60 °C and 19 mmHg until the inorganic salt began to precipitate. The concentrated product was extracted with ethyl acetate (5 mL × 3), and the organic phases were combined and dried over anhydrous sodium sulfate. The dried organic phase was concentrated under reduced pressure and the residue was further dried under reduced pressure to give white crystals of 3-amino-5-methoxyisoxazole (1.63 g, 70.6% yield). The melting point of the product was 82-83 °C (hexane-ethyl acetate recrystallization). NMR hydrogen spectrum (CDCl3) data: δ 3.93 (5H, broad peak, CH3 + NH2), 4.81 (1H, single peak, H-4); NMR hydrogen spectrum (CDCl3 + D2O) data: δ 3.93 (3H, single peak, CH3), 4.83 (1H, single peak, H-4). Infrared spectra (CHCl3) major absorption peaks: 3840, 1628, 1487 cm-1. Elemental analysis (calculated values, C4H6N2O2): C, 42.11%; H, 5.30%; N, 24.55%. Measured values: C, 41.74%; H, 5.06%; N, 24.35%. |