Methanamine, N-methoxy-, hydrochloride (1:1) → 2-fluoro-N-methoxy-N,5-dimethylnicotinamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-fluoro-5-methylnicotinic acid (4.9 g, 31.6 mmol), N,O-dimethylhydroxylamine hydrochloride (4.01 g, 41.08 mmol), diisopropylethylamine (12.6 ml, 72.68 mmol) in dichloromethane (150 ml) at 0° C. was added TBTU (11.16 g, 34.76 mmol) portionwise over 30 minutes. The solution was stirred at 0° C. for a further 10 minutes then, at room temperature for 18 hours. The reaction mixture was washed with a 10 wt % solution of citric acid and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-20% EtOAc/Petrol) to afford the title compound as a colourless solid (5.44 g, 87% yield).

Provenance & Evidence