Methylamine → 2-amino-4-fluoro-N-methylbenzamide

Participants

Reaction Steps

Carbonyl-1,1′-diimidazole (1.26 g) was added to 2-amino-4-fluorobenzoic acid (1.0 g) in THF (16.3 mL). After stirring overnight a solution of methylamine in THF (2M, 4.9 mL) was added and the reaction stirred for 3 hours. The reaction was concentrated in vacuo and the residue dissolved in EtOAc (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The phases were separated and the organics were washed with water (2×100 mL) and then saturated aqueous brine (30 mL). The organics were dried (MgSO4, 15 g), filtered and concentrated in vacuo to give crude product (0.9 g). This material was purified by column chromatography (SiO2, 40 g, eluent 3% MeOH in DCM) to give 2-amino-4-fluoro-N-methylbenzamide (0.6 g). 1H NMR spectrum (270 MHz, DMSO): 2.69 (d, 3H), 6.28 (ddd, 1H), 6.42 (dd, 1H), 6.74 (bs, 2H), 7.48 (dd, 1H), 8.16 (q, 1H); Mass spectrum: ESI+ MH+ 169.

Provenance & Evidence