Hydrofluoric Acid → 4-((5-Chloro-3-fluoro-2-pyridinyl)oxy)phenol

Participants

Reaction Conditions

Reaction Steps

122.5 g (0.518 mole) of 4-(3-amino-5-chloropyridin-2-yloxy)phenol are introduced at -8° to 0° C. into a vessel charged with 400 g (20 moles) of hydrogen fluoride. Then 37.3 g (0.540 mole) of sodium nitrite are added in portions over one hour. The mixture is stirred for 2 hours at 0° C. and slowly heated to 55° C. in an autoclave. Excess hydrogen fluoride is removed by distillation and the residue is taken up in 200 ml of methylene chloride and the solution is neutralised with ice-water and ammonia, the organic phase is dried and concentrated by evaporation, affording 112 g of 4-(5-chloro-3-fluoropyridin-2-yloxy)phenol with a melting point of 97°-98° C.

Provenance & Evidence