Benzylamine → N-benzyl-2-chloro-6-methoxyisonicotinamide

Participants

Reaction Steps

To a solution of 2-chloro-6-methoxyisonicotinic acid (4.90 g, 26.00 mmol, prepared according to Okajima S., Yakugaku Zasshi, (1953), 73, 845-847) and 4-methylmorpholine (3.3 mL, 30.00 mmol) in tetrahydrofuran (100 mL) was added isobutyl chloroformate (3.8 mL, 28.00 mmol) at 0° C. The resulting solution was stirred at ambient temperature for 1 hour, followed by the addition of benzylamine (4.2 mL, 38.00 mmol). The reaction mixture was stirred at ambient temperature for 20 hours, diluted with ethyl acetate (100 mL), washed with water (30 mL) and brine (30 mL). The organic solution was dried over anhydrous sulphate, filtered and concentrated in vacuo. The residue was recrystallized from ethyl acetate and hexanes to give N-benzyl-2-chloro-6-methoxyisonicotinamide (6.20 g, 86%): 1H NMR (300 MHz, CDCl3) δ 7.37-7.27 (m, 5H), 7.18 (s, 1H), 6.94 (s, 1H), 6.43 (br s, 1H), 4.58 (d, J=5.7 Hz, 2H), 3.94 (s, 3H); MS (ES+) m/z 277.4 (M+1).

Provenance & Evidence