6-Bromo-5-fluoro-2-pyridinecarboxylic acid

Synthesis of 6-bromo-5-fluoropicolinic acid Synthesis of 6-bromo-5-fluoropicolinic acid[00144] To 2-bromo-3-fluoro-6-methylpyridine (1.0 equiv.) in HStep A: Preparation of 6-bromo-5-fluoropicolinic acid: 2-Bromo-3-fluoro-6- methylpyridine (3.60 g, 18.9 mmol) was dissolved in 10 mL of pyridine in pressure tube. To this was added 50 mL of water, and the mixture was warmed to 85 °C. Potassium permanganate (5.99 g, 37.9 mmol) was added, the tube was capped, and the mixture was stirred at 85 °C for 48 hours. The mixture was filtered through GF/F filter paper, and the filtrate was concentrated to about half volume under reduced pressure. The remaining material was acidified to pH 4 with 1M aqueous HC1 and extracted with EtOAc. The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to give 0.70 g of the title compound (17percent).Synthesis of 6-bromo-5-fluoropicolinic acidTo 2-bromo-3-fluoro-6-methylpyridine (1.0 equiv.) in HTo 2-bromo-3-fluoro-6-methylpyridine (1.0 equiv.) in HSynthesis of 6-bromo-5-fluoropicolinic acid To 2-bromo-3-fluoro-6-methylpyridine (1.0 equiv.) in HSynthesis of 6-bromo-5-fluoropicolinic acid To 2-bromo-3-fluoro-6-methylpyridine (1.0 equiv.) in HPotassium permanganate (2.50 g, 15.8 mmol) was added portionwise to asuspension of 2-bromo-3-fluoro-6-methylpyridine (1 g, 5.26 mmol) in water (22 ml) at 90 00The reaction was stirred for 3 hours and then filtered through Celite® while hot, washing with hot water. The filtrate was acidified to pH 1 via addition of 6 N HCI. The resultant precipitate was collected by filtration to give the title compound (0.15 g, 13 percent yield). MS (mlz) 219.9 (M+H).To a stirred solution of(S)-(1-(aminomethyl)-6-chloro-1, 2, 3, 4- tetrahydronaphthalen-1-yl)methanol hydrochloride (150 g, 572 mmol) was dissolved in dry DMSO (2250 mL) under a nitrogen atmosphere at roomtemperature. The solution was treated with