Synthesis
To a stirred solution of (tert-butoxycarbonyl)glycine (5.0 g, 28.57 mmol) and triethylamine (4.1 mL, 31.42 mmol) in dichloromethane (80 mL) was added N,O-dimethylhydroxylamine hydrochloride (3.0 g, 31.42 mmol). Subsequently, the reaction mixture was stirred at room temperature for 12 hours by dropwise addition of a solution of N,N'-dicyclohexylcarbodiimide (6.5 g, 31.42 mmol) in dichloromethane (20 mL). The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was filtered through diatomaceous earth and washed with dichloromethane. The filtrate was concentrated under reduced pressure to give the crude product, which was purified by silica gel column chromatography using 10% ethyl acetate/hexane as eluent to give the final N-BOC-glycine-N'-methoxy-N'-methylamide (6.0 g, 97.0%) as an off-white solid.1H NMR (400 MHz, CDCl3): δ 5.27 (broad single peak, 1H), δ 4.08 (broad single peak, 2H), 3.72 (single peak, 3H), 3.21 (single peak, 3H), 1.46 (single peak, 9H).
References
[1] Patent: WO2018/165520, 2018, A1. Location in patent: Page/Page column 226-227
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 12, p. 2180 - 2183
[3] Journal of Organic Chemistry, 2006, vol. 71, # 17, p. 6678 - 6681
[4] Nucleosides, Nucleotides and Nucleic Acids, 2001, vol. 20, # 4-7, p. 1393 - 1397
[5] Arzneimittel-Forschung/Drug Research, 1989, vol. 39, # 4, p. 432 - 437
