1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → tert-Butyl 4-({[(2-chloro-5-fluoropyridin-3-yl)carbonyl]amino}methyl)benzoate

Participants

Reaction Steps

To a stirred solution of 2-chloro-5-fluoronicotinic acid (2.0 g, 10 mmol) and tert-butyl 4-(aminomethyl)benzoate (1.65 g, 8 mmol) in dichloromethane (25 mL) were successively added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (2.88 g, 15 mmol), 1-hydroxybenzotriazole hydrate (HOBT) (1.53 g, 10 mmol), and triethylamine (5 mL). After being stirred overnight, the reaction mixture was poured into water (100 mL). The organic layer_was separated and the aqueous layer was extracted with dichloromethane (50 mL×2). The combined organic layers were washed with brine (100 mL), dried (sodium sulfate), and evaporated. The residue was purified by flush column chromatography on silica gel (200 g) eluting with dichloromethane/ethyl acetate (20/1) to afford 2.39 g (82%) of the title compounds as white solids: 1H-NMR (CDCl3) δ 8.33 (1H, d, J=3.1 Hz), 7.97 (2H, d, J=8.4 Hz), 7.91 (1H, dd, J=7.9, 3.1 Hz), 7.40 (2H, d, J=8.4 Hz), 7.04 (1H, br.s), 4.70 (2H, d, J=5.9 Hz), 1.58 (9H, s).

Provenance & Evidence