Hydrochloric Acid → Methyl 2-chloro-6-(methylamino)isonicotinate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-chloro-6-(methylamino)isonicotinic acid (18.1 g, 97 mmol) in 600 mL MeOH was added thionyl chloride (7.783 mL, 107 mmol) very slowly (emits HCl gas violently). Reaction refluxed to 65° C. for 2 h. After 2 h, reaction was concentrated in vacuo. The residue was dissolved in EtOAc (400 mL) and neutralized with saturated NaHCO3 solution (300 mL). The aqueous solution was extracted with EtOAc (150 mL×3). The combined organics were washed with brine (150 mL), dried over Mg2SO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (5% EtOAc/hexanes, then 20% EtOAc/hexanes) yielded 11.3 g (58%) of methyl 2-chloro-6-(methylamino)isonicotinate as a yellow brown solid. 1H NMR (CDCl3, 400 mHz) 7.08 (d, J=0.91 Hz, 1H); 6.84 (d, J=0.73 Hz, 1H); 5.09 (s, NH); 3.92 (s, 3H); 2.96 (d, J=5.31 Hz, 3H); LC/MS [M+H]+=201.0.

Provenance & Evidence