Triethylamine → 2,6-Dichloropyridine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A dry mixture of powdered 3-cyano-6-hydroxy-pyridin-2-ol anion, sodium salt (102.34 g, 0.648 mol), as prepared in the previous step, and triethylamine hydrochloride (89.20 g, 0.648 mol) was swirled until the two components appeared completely mixed. This dry mixture was then cooled on an ice bath while POCl3 (150 mL, 1.62 mol) was slowly poured in under air with intermittent swirling. Triethylamine (90.3 mL, 0.648 mol) was then added rapidly in 2 mL portions with frequent manual swirling while cooling on an ice bath. The flask containing the resulting warm dark semi-solid was then fitted with a reflux condenser and CaSO4 drying tube and stirred under air at 140° C. for 20 h. The easily stirred dark brown thick “solution” was then allowed to cool to rt, chilled on an ice bath, diluted with ether (800 mL), and washed with ice (800 mL). The very dark organic layer was washed with ice water (1×1 L), and the aqueous layers were combined and extracted with ether (3×1 L). The combined ether extracts were concentrated under reduced pressure to give a wet orange-brown solid. This was dissolved in DCM (1 L), dried (2×Na2SO4), and concentrated under reduced pressure at 60° C. to afford the title compound as a brown solid (80.7 g, 466 mmol).

Provenance & Evidence