tert-butyl (1-[Methoxy(Methyl)aMino]-1-oxopent-4-yn-2-yl)carbaMate

Synthesis

2-((tert-butoxycarbonyl)amino)pent-4-ynoic acid (33 g, 0.155 mol) was dissolved in N,N-dimethylformamide (200 ml) and the reaction temperature was kept below 10 °C. Subsequently, N,N'-carbonyldiimidazole (32.58 g, 0.201 mol) was added to the reaction solution and the reaction was carried out at 0 °C for 1 hour. Next, N,O-dimethylhydroxylamine hydrochloride (19.6 g, 0.186 mol) was added and the reaction mixture was stirred at room temperature overnight. After the reaction was completed, water (150 ml) was added slowly and stirring was continued for 1 hour. The reaction mixture was extracted with ethyl acetate (100 ml) and the organic phases were combined. The organic phase was washed sequentially with saturated sodium bicarbonate solution (60 ml) and saturated sodium chloride solution (60 ml), followed by addition of anhydrous magnesium sulfate to dry. The desiccant was removed by filtration, the filtrate was concentrated and purified by column chromatography (petroleum ether/ethyl acetate, v/v=10:1) to afford the white solid product (tert-butyl 1-(methoxy(methyl)amino)-1-oxopent-4-yn-2-yl)carbamate (35 g, 88.2% yield). Mass spectrum (ESI) m/z: 156.9 [M-99].

References

[1] Organic Letters, 2010, vol. 12, # 4, p. 684 - 687
[2] Patent: EP3159344, 2017, A1. Location in patent: Paragraph 0096; 0097; 0100
[3] Patent: TW2017/8221, 2017, A. Location in patent: Page/Page column 33; 34
[4] Patent: TW2017/8220, 2017, A. Location in patent: Page/Page column 56; 57; 58
[5] Patent: TW2017/8222, 2017, A. Location in patent: Paragraph 34; 35