1,2-Dichloroethane → 2-Fluoro-N-methoxy-N-methylnicotinamide

Participants

Reaction Conditions

Reaction Steps

2-fluoropyridine-3-carboxylic acid (100 g, 708.7 mmol) was dissolved in THF (1.5 L). DMAP (86.58 g, 708.7 mmol) was added followed by N-methoxymethanamine hydrochloride (76.05 g, 779.6 mmol). The mixture was cooled to 10° C. then DIPEA (100.8 g, 135.8 mL, 779.6 mmol) was added followed by EDC (149.5 g, 779.6 mmol) portionwise. The mixture was stirred for 30 minutes, then warmed rapidly to ambient temp (22° C.) and stirred overnight. Lc/Ms after this time showed no acid remaining. The reaction mixture was diluted with ethyl acetate (1 L) and water (1.5 L). The mixture was stirred for 10 minutes then the organic phase was isolated. The aqueous was extracted with ethyl acetate (2×500 ml) and the combined organics washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude was purified through a silica plug, eluting with 50-70% ethyl acetate/petrol. This afforded the title compound as a pale yellow oil (81 g, 62%); 1H NMR (CDCl3) 3.39 (3H, s), 3,68 (3H, brs), 7.29 (1H, m), 7.92 (1H, m), 8.32 (1H, m); MS ES (+) 184.9 (M+1).

Provenance & Evidence