Synthesis
GENERAL STEPS: To a configured aqueous sodium hydroxide solution (40.00 g, 1 mol, dissolved in 200 mL of water) were sequentially added hydroxylamine hydrochloride (24.00 g, 346 mmol) and 4,4-dimethyl-3-oxovaleronitrile (40.00 g, 320 mmol). The reaction mixture was stirred at a constant temperature at 50 °C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature and the precipitated white crystalline solid was collected by filtration. The solid was washed several times with cold water and subsequently dried to afford the target compound 3-tert-butylisoxazol-5-amine as a white crystalline solid (34 g, 76% yield). The product was characterized by 1H NMR (DMSO-d6): δ 6.41 (brs, 2H), 4.85 (s, 1H), 1.18 (s, 9H); LC-MS (ES, m/z) analysis showed that the [M + H]+ peak was located at 141.3.
References
[1] Heterocycles, 1991, vol. 32, # 6, p. 1153 - 1158
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 3, p. 1082 - 1105
[3] Patent: US2008/261961, 2008, A1. Location in patent: Page/Page column 16
[4] Organic Letters, 2018, vol. 20, # 9, p. 2774 - 2777
[5] Journal of Medicinal Chemistry, 2016, vol. 59, # 18, p. 8293 - 8305
