Methyl 5-amino-2-chloroisonicotinate

Synthesis

67-56-1

171178-46-4

1073182-59-8

To a stirred solution of 5-tert-butoxycarbonylamino-2-chloroisonicotinic acid (crude, 8.0 g) in methanol (50 mL) was slowly added concentrated sulfuric acid (5.0 mL). The reaction mixture was heated to reflux and kept at this condition for the reaction overnight. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently concentrated under reduced pressure to remove the solvent. The concentrated residue was diluted with an appropriate amount of water and then neutralized with saturated sodium bicarbonate solution to pH=8. The neutralized aqueous phase was extracted with ethyl acetate (100 mL x2). The organic phases were combined and washed with saturated brine (50 mL), followed by drying with anhydrous sodium sulfate and filtration. The filtrate was evaporated to dryness under reduced pressure and the resulting crude product was purified by silica gel column chromatography.

References