Phosphorus oxychloride → 6-Chloropyrimidine-4-carbonitrile

Participants

Reaction Steps

6-Hydroxy-4-pyrimidinecarboxamide (Intermediate 7, 563 mg, 4.05 mmol) was taken up in phosphorus oxychloride (3.9 mL, 41.8 mmol) and the resulting mixture was heated under reflux for 18 hours. The reaction mixture was allowed to cool to room temperature and evaporated under reduced pressure. The residue was poured into ice cooled water, neutralised with 0.88 ammonia solution and extracted with ethyl acetate (×3). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-20% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil (346 mg);

Provenance & Evidence