Methanamine, N-methoxy-, hydrochloride (1:1) → 2-Fluoro-N-methoxy-N-methylnicotinamide

Participants

Reaction Steps

TBTU coupling agent (13 g, 40 mmol) was added to a solution of 2-fluoronicotinic acid (5.6 g, 40 mmol), N-methoxy-N-methylamine hydrochloride (4.4 g, 45 mmol) and diisopropylethylamine (16 ml, 0.1 mol) in dichloromethane (100 ml) under nitrogen. The reaction mixture was stirred at room temperature for eighteen hours. It was diluted with more dichloromethane (200 ml), washed with a 2M aqueous hydrochloric acid solution (50 ml), a saturated sodium bicarbonate solution (100 ml), and brine (100 ml). The organic was dried over magnesium sulfate and, after filtration, concentrated in vacuo. The residue was purified by flash chromatography (120 g SiO2, pentane/ethyl acetate) to afford the title compound as a colourless oil (6 g, 80%). 1H NMR (CDCl3): 3.40-3.45 (3H, s), 3.55-3.65 (3H, s), 7.75-7.80 (1H, t), 7.90-7.95 (1H, t), 8.28-8.30 (1H, d).

Provenance & Evidence