Triethylamine → 2-chloro-5-iodo-N,N-dimethylnicotinamide

Participants

Reaction Steps

A solution of 2-hydroxynicotinic acid (7.17 g, 51.5 mmol) in 100 mL of DMF was treated with N-iodosuccinimide (12.76 g, 56.7 mmol) for approximately 64 hours. The mixture was concentrated under reduced pressure and the residue was suspended in approximately 70 mL of dichloroethane. Thionyl chloride (15 mL, 20.8 mmol) was slowly added to the suspension and the mixture was heated at reflux for 2 hours. The mixture was distilled until approximately 70 mL of distillate was collected. The residue was allowed to cool to room temperature and then dissolved in 70 mL of methylene chloride. The solution was cooled under nitrogen to 0° C. and treated with triethylamine (23 mL, 156 mmol). Dimethylamine hydrochloride (4.6 g, 56 mmol) was added and the mixture was stirred at approximately 0° C. for 0.5 hours. The mixture was filtered and the filtrate was partitioned between aqueous sodium bicarbonate and methylene chloride. The methylene chloride layer was separated, washed with brine, dried (Na2SO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with hexanes/ethyl acetate (5:1) to give 2-chloro-5-iodo-N,N-dimethyl-nicotinamide (5.17 g, 16.7 mmol).

Provenance & Evidence