2-Chloro-6-fluoro-3-methoxybenzoic acid → N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-2-chloro-6-fluoro-N-(2-hydroxyethyl)-3-methoxybenzamide

Participants

Reaction Steps

To a solution of 2-chloro-6-fluoro-3-methoxy-benzoic acid (1.00 g, 4.89 mmol) in anhydrous DMF (30 mL) were added HATU (2.30 g, 5.85 mmol) and TEA (1.36 mL, 9.76 mmol). The reaction mixture was stirred for 5 minutes, then 2-[(2-benzyloxy-4,6-dimethyl-pyridin-3-ylmethyl)-amino]-ethanol (Cpd KK, 1.47 g, 5.12 mmol) was added as a solid in one portion. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between ethyl acetate (200 mL) and water (200 mL). The organic phase was separated, washed with brine (2×200 mL), dried over sodium sulfate, and concentrated under vacuum to give N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-2-chloro-6-fluoro-N-(2-hydroxyethyl)-3-methoxybenzamide (124a, 2.31 g, 100%) as a gum.

Provenance & Evidence