Thionyl Chloride → 6-Chloronicotinoyl Chloride

Participants

Reaction Steps

To 7.88 g of 6-chloronicotinic acid were added 7.3 ml of thionyl chloride and a few drops of DMF. The mixture was heated under reflux for 2 hours, and then the excess of thionyl chloride was distilled off to give crystals of 6-chloronicotinoyl chloride. A solution of the crystals in 60 ml of tetrahydrofuran was added dropwise to a solution of 15.47 g of 5-aminopentanol in 200 ml of tetrahydrofuran at a temperature below 0° C. The mixture was stirred overnight while gradually raising the temperature to room temperature. The solvent was distilled off and to the residue was added water followed by extraction with ethyl acetate. Then, the extract was washed successively with water and a saturated brine solution, dried over magnesium sulfate. The solvent was distilled off and the residue was recrystallized from ethyl acetate to give 11.24 g of N-(5-hydroxypentyl)-6-chloronicotinamide (yield 93%).

Provenance & Evidence