2-chloro-3-fluoro-1-oxidopyridin-1-ium

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-chloro-3-fluoropyridine N-oxide (400 mg, 3.0 mmol) and piperazine (1.3 g, 15 mmol) in n-butanol, 15 ml, is stirred at reflux for 20 hours. After concentrating under reduced pressure at 55°-60° C., the residue is chromatographed over silica gel and the crude N-oxide eluted with a 50% methanol-methylene chloride solvent mixture. The appropriate eluate is concentrated to an oily residue of the title compound. at reflux for 20 hours After concentrating under reduced pressure at 55°-60° C. the residue is chromatographed over silica gel the crude N-oxide eluted with a 50% methanol-methylene chloride solvent mixture The appropriate eluate is concentrated to an oily residue of the title compound

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-3-fluoropyridine (11.8 g, 0.10 mol) and 11.4 ml of 30% hydrogen peroxide in acetic acid, 70 ml, is stirred at 75° C. for 4 hours. Additional 30% hydrogen peroxide, three 5 ml portions, is added over 24 hours followed by 3 ml of a saturated sodium bisulfite solution. The reaction mixture is concentrated to approximately 25 ml under reduced pressure at 55°-60° C., diluted with water, 30 ml, and made basic with potassium carbonate. The crude N-oxide is extracted into ethyl acetate, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography over silica gel and elution with 2% MeOH- 98% CHCl3 (v/v) mixture gives 2-chloro-3-fluoropyridine N-oxide as a liquid. The reaction mixture is concentrated to approximately 25 ml under reduced pressure at 55°-60° C. diluted with water, 30 ml The crude N-oxide is extracted into ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure Chromatography over silica gel and elution with 2% MeOH- 98% CHCl3 (v/v) mixture