Diethyl Ether → 5-Acetyloxy-2-chloropyridine

Participants

Reaction Conditions

Reaction Steps

48% Aqueous tetrafluoroboric acid (40.5 mL) was added to the above-obtained 5-amino-2-chloropyridine (18 g) in ethanol (360 mL), and under cooling at −5° C., tert-butyl nitrite (23.5 mL) was added dropwise to the resultant mixture, followed by stirring for 20 minutes. Diethyl ether was added to the reaction mixture, and the precipitated product was recovered by filtration, followed by drying, to thereby give 6-chloropyridine-3-diazonium tetrafluoroborate (32 g, quantitative amount). The thus-obtained diazonium salt (32 g) in acetic anhydride (160 mL) was heated gradually to 90° C., and the mixture was stirred for 45 minutes, and then cooled in air. The reaction solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water. The organic layer was sequentially washed with water and saturated brine, and then dried over magnesium sulfate anhydrate, followed by filtration. The solvent was removed under reduced pressure, and the residue was purified through silica gel chromatography (hexane-ethyl acetate), to thereby give 5-acetoxy-2-chloropyridine as a solid (10 g, 42%).

Provenance & Evidence