Triethylamine → Ethyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-(difluoromethyl)nicotinate

Participants

Reaction Steps

Combine ethyl 5-(aminomethyl)-2-(difluoromethyl)pyridine-3-carboxylate hydrochloride (17.849 mmol, 4.760 g), THF (180 mL) and tert-butoxycarbonyl tert-butyl carbonate (21.419 mmol, 4.675 mL). Stir the mixture at room temperature for about 10 minutes. Add triethylamine (5.225 mL, 37.484 mmol), and stir at room temperature 16 hours. Remove the solids by vacuum filtration, and rinse with EtOAc. Concentrate the filtrate under reduced pressure. Purify the resulting yellow oil by silica gel chromatography (220 g RediSep® silica gel column) eluting with a gradient of 5-45% EtOAc gradient in hexane to give the title compound (3.62 g, 68% yield) as a light yellow crystalline solid. 1H NMR (399.80 MHz, d6-DMSO) δ 8.71 (d, J=2.1 Hz, 1H), 8.15-8.13 (m, 1H), 7.56-7.24 (m, 2H), 4.33 (q, J=7.1 Hz, 2H), 4.24-4.21 (m, 2H), 1.36 (s, 9H), 1.30 (t, J=7.1 Hz, 3H). LCMS (m/z) 331 (M+1).

Provenance & Evidence