3-Bromo-6-fluoropicolinic acid

5-bromo-2-fluoro-6-methylpyridine (5kg) was dissolved in concentrated sulfuric acid (50kg).After the reaction was warmed to 60 ° C, CrO3 (16 kg) was added in portions. After the addition was completed, the reaction was continued for 18 hours. TLC monitors the reaction. After the reaction was completed, the reaction was neutralized by adding NaOH (20percent) to neutrality. Further ethyl acetate extraction (50 L X 3) was added.After combining the extracts, they were dried and concentrated. The crude product obtained was beaten with n-hexane. Filter and dry to obtain pure 3-bromo-6-fluoropicolinic acid (3.8 kg, yield 58percent).Water (1600 mL) was added to 3-bromo-6-fluoro-2-methylpyridine (60 g, 0.32 mol), mechanically stirred and heated to reflux , potassium permanganate (220 g, 1.4 mol) was added to the flask in 11 portions at intervals of 15 min, after the addition, the reflux was continued for 5 h. The reaction solution was cooled to room temperature, suction filtered, and the filtrate was adjusted to pH 5 with dilute hydrochloric acid, then, the filtrate was spun dry, and then anhydrous ethanol (500 ml) was added thereto, and the mixture was stirred under reflux for 30 min, filtered while hot, and the filtrate was dried to give 3-bromo-6-fluoro-2-picolinic acid (31 g, 45percent).Thionyl chloride (200 ml) was slowly added to 5-bromo-2-fluoro-6-methylpyridine (5kg) was dissolved in concentrated sulfuric acid (50kg).After the reaction was warmed to 60 C, CrO3 (16 kg) was added in portions. After the addition was completed, the reaction was continued for 18 hours. TLC monitors the reaction. After the reaction was completed, the reaction was neutralized by adding NaOH (20%) to neutrality. Further ethyl acetate extraction (50 L X 3) was added.After combining the extracts, they were dried and concentrated. The crude product obtained was beaten with n-hexane. Filter and dry to obtain pure Water (1600 mL) was added to 3-bromo-6-fluoro-2-methylpyridine (60 g, 0.32 mol), mechanically stirred and heated to reflux , potassium permanganate (220 g, 1.4 mol) was added to the flask in 11 portions at intervals of 15 min, after the addition, the reflux was continued for 5 h. The reaction solution was cooled to room temperature, suction filtered, and the filtrate was adjusted to pH 5 with dilute hydrochloric acid, then, the filtrate was spun dry, and then anhydrous ethanol (500 ml) was added thereto, and the mixture was stirred under reflux for 30 min, filtered while hot, and the filtrate was dried to give Example 1.75.7 (4.22 g), and potassium carbonate (1.53 g) were stirred in 60 mL tetrahydrofuran, 25 mL methanol, and 10 mL water overnight. The mixture was concentrated and 60 mL N, N-dimethylformamide was added. To this was then added Example 1.1.9 (3.05 g) and triethylamine (5 mL), and the reaction was stirred at 60 C. overnight. The mixture was cooled to room temperature, poured into ethyl acetate (600 mL), washed with water (3*) and brine, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on silica gel using 5-50% ethyl acetate in heptanes to give the title compound. MS (ESI) m/e 618.2 (M+H)+.

Molecular Weight:220.00
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:218.93312
Monoisotopic Mass:218.93312
Topological Polar Surface Area:50.2
Heavy Atom Count:11
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes