Synthesis
To a solution of dichloromethane (60 mL) containing N,O-dimethylhydroxylamine hydrochloride (10.0 g, 95.69 mmol, 1.0 eq.) and triethylamine (19.36 g, 191.6 mmol, 2.0 eq.), the reaction mixture was stirred at 0 °C for 30 min. Subsequently, cyclopropanecarbonyl chloride (Compound 96.1) was slowly added at the same temperature. The reaction mixture was transferred to room temperature and continued stirring for 15 hours. After completion of the reaction, the organic layer was washed sequentially with water, brine, saturated sodium bicarbonate solution and 1.0 N hydrochloric acid, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Finally, the crude product was purified by column chromatography to afford N-methoxy-N-methylcyclopropane carboxamide (Compound 96.2, 9.0 g, 72.9% yield).
References
[1] Journal of Medicinal Chemistry, 2017, vol. 60, # 12, p. 4840 - 4860
[2] Patent: WO2017/40757, 2017, A1. Location in patent: Paragraph 00466-00467
[3] Patent: US2005/197337, 2005, A1. Location in patent: Page/Page column 10
[4] Patent: WO2005/94828, 2005, A1. Location in patent: Page/Page column 19
[5] Patent: WO2008/34860, 2008, A1. Location in patent: Page/Page column 139
