Hydrochloric Acid → Ethyl 5-(aminomethyl)-2-(difluoromethyl)nicotinate hydrochloride

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Reaction Steps

Purge a mixture of methyl 5-cyano-2-(difluoromethyl)pyridine-3-carboxylate (160 g, 707.4 mmol) and EtOH (2 L) with nitrogen and stir 15 min. Add hydrochloric acid (37 wt % aqueous, 273 mL, 3183.2 mmol, 4.5 equiv) and palladium (5% on carbon, 48 g, 22.5 mmol, 0.031 equiv) in EtOH (100 mL), and stir the resulting suspension under 60 psi of hydrogen at room temperature for 70 min. Remove the solids by filtration over diatomaceous earth; wash the solid cake with EtOH (1 L); and concentrate the filtrate under reduced pressure. Repeat this procedure twice; combine the solids; and slurry in Et2O:DCM [10:1, 5.5 L]. Filter the solids and dry the resulting material at 45° C. for 3 hours to give the title compound as a light brown solid (714 g, 96% yield). MS (m/z) 216 (M+1).

Provenance & Evidence