Phosphorus oxychloride → 4-Chloro-6-fluoroquinoline

Participants

Reaction Steps

A mixture of 52 g (0.319 mol) of 6-fluoro-4-hydroxyquinoline and 100 ml of phosphorus oxychloride was stirred and heated under reflux for 3 hr. The reaction mixture was concentrated in vacuo. A slurry of the residue in methylene chloride was poured into ice-water, and the mixture neutralized with 3N sodium hydroxide. The organic phase was separated, and the aqueous phase was extracted with 250 ml of methylene chloride twice. The organic phases were combined, washed with water, dired over sodium sulfate, and concentrated in vacuo. The residue was crystallized from hexane to give 27.95 g of product, mp 71°-74°.

Provenance & Evidence