Water → 6-Fluoronicotinic Acid

Participants

Reaction Steps

To a solution of 2-amino-5-methylpyridine (75 g, 693 mmol) in 42% tetrafluoroboric acid (291 ml) was added a solution of sodium nitrite (47.8 g, 693 mmol) in water (100 ml) while cooling with dry ice-acetone so that the inside temperature would not exceed 10° C. After the reaction solution was stirred at 45° C. for 30 min., 8N aqueous sodium hydroxide solution (100 ml) was gradually added, and the mixture was extracted with diethyl ether (300 ml×2). The extract was concentrated under reduced pressure and the residue was distilled away to give 2-fluoro-5-methylpyridine (30.4 g). A solution of potassium permanganate (100 g, 632 mmol) in water (1.2 L) was heated to 80° C. and 2-fluoro-5-methylpyridine (30.4 g, 274 mmol) was added. The mixture was heated under reflux for 4.5 hrs. Insoluble material was filtered off with celite from the reaction solution, and the filtrate was concentrated to 200 ml. Then, 6N hydrochloric acid was added until the pH became about 3. The precipitated crystals were collected by filtration to give 6-fluoro-3-pyridinecarboxylic acid (10.58 g, 11%).

Provenance & Evidence