Thioanisole → 4-Chloro-7-fluoro-6-hydroxy-3-quinolinecarbonitrile

Participants

Reaction Steps

A mixture of 6-benzyloxy-4-chloro-7-fluoro-3-quinolinecarbonitrile (733 mg, 2.34 mmol) and 1 mL of thioanisole in 12 mL of trifluoroacetic acid is heated at reflux for 9 hours then concentrated in vacuo. The residue is treated with ice water and then basified to pH 9-10 by the addition of aqueous ammonium hydroxide. The resultant solid is collected by filtration and washed with diethyl ether. The filtrate is extracted with 10% methanol in ethyl acetate. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is combined with the solid obtained initially, and this material is dissolved in 5% methanol in ethyl acetate and absorbed onto silica gel. Purification by flash column chromatography eluting with a gradient of hexane to increasing amounts of ethyl acetate in hexane to 5% methanol in ethyl acetate provides 260 mg of 4-chloro-7-fluoro-6-hydroxy-3-quinolinecarbonitrile, mp>250° C.

Provenance & Evidence