2-CHLORO-5-FLUORO-3-NITROPYRIDINE

light powder

a) PREPARATION 53A mixture of the pyridine of preparation 55 (105 mg, 0.66 mmol), phosphorus oxychloride (1 ml) and Λ/, Λ/-dimethyIformamide (10 μl, catalytic) was heated at 11OIn a high-pressure reactor, 85 g (0.5 mol) of 2, 3-dichloro-5-fluoropyridine was added to 200 mL of ammonia water.Set the temperature to 180 °C, high pressure reaction 24h, TLC detects the reaction of the raw material completely.The solvent was evaporated to give 2-chloro-5-fluoro-3-aminopyridine 65 g;2-chloro-5-fluoro-3-aminopyridine 65 g (0.45 mol)Placed in 900 mL round bottom flask in acetonitrile, Aqueous buffer solution 450mL (0.6M K2CO3-4x10-4M EDTA disodium salt) was added successively, Acetonitrile 350mL (3mol) and 30percent H2O2 in water290mL (3mol), The reaction mixture was stirred at room temperature for 1 hour and extracted with ethyl acetate (3 x 300 mL).Combine organic layers, Dry with anhydrous Na2SO4, Remove the solvent under vacuum to obtain the product of sufficient purity 2-chloro-5-fluoro-3-nitropyridine65g;To a solution of 2-chloro-5-fluoro-3-nitropyridine 65 g (0.35 mol) in DMSO/H2O (9:1, 3500 mL) was added L-Proline 230g (2mol), Na2CO3 210g (2mol), NaN3 230g (3.5mol), Sodium ascorbate 350g (1.75mol) andCuSO4·5H2O500g (2 mol);The mixture was stirred in an oil bath at 70 °C for 24 hours.Then pour the mixture into 10, 000 mL of ice water.The solid product was filtered and crystallized to obtain 47 g of 2-amino-5-fluoro-3-nitropyridine.Suggest an editExample 1See also1In a high-pressure reaction vessel, 2, 3-dichloro-5-fluoropyridine 85g (0.5 mol) was added to 200 mL of ammonia water, and the temperature was set at 180° C., and the reaction under high pressure was performed for 24 h. The reaction of the starting material was complete by TLC, and the solvent was swirled to obtain 2- Chloro-5-fluoro-3-aminopyridine 65g;Place 2-chloro-5-fluoro-3-aminopyridine 65 g (0.45 mol) in a 900 mL round-bottomed flask in acetonitrile, and add 450 mL of water buffer solution (0.6 M K2CO3-4×10-4 M EDTA disodium salt). 350 mL (3 mol) of acetonitrile and 290 mL (3 mol) of a 30percent H2O2 aqueous solution, and the reaction mixture was stirred at room temperature for 1 hour and extracted with ethyl acetate (3 x 300 mL). The organic layers were combined and dried over anhydrous Na2SO4. The solvent was removed to give a sufficiently pure product, 2-chloro-5-fluoro-3-nitropyridine, 65 g;To a solution of 65 g (0.35 mol) of 2-chloro-5-fluoro-3-nitropyridine in DMSO/H2O (mass ratio 9:1, 3500 mL) was added L-proline 230 g (2 mol), Na2CO3 210 g (2 mol), NaN3 230 g (3.5 mol), sodium ascorbate 350 g (1.75 mol) and CuSO4.5H2O 500 g (2 mol); the mixture was stirred in an oil bath at 70C for 24 hours, and then the mixture was poured into 5000 mL of ice water to give a solid product. Filter and crystallize to obtain 47g of 2-amino-5-fluoro-3-nitropyridine; add 2-amino-5-fluoro-3-nitropyridine to the aqueous solution of sulfuric acid, add a certain amount of chloroacetic acid, and heat to 120°C. After TLC monitored the reaction of the raw materials, the reaction mixture was extracted with methylene chloride. The pH of the organic phase was adjusted to 7-8 with a saturated sodium carbonate solution, and the organic phase was concentrated to obtain 2-amino-5-fluoro-pyridine.

Molecular Weight:176.53
XLogP3:1.7
Hydrogen Bond Acceptor Count:4
Exact Mass:175.9788832
Monoisotopic Mass:175.9788832
Topological Polar Surface Area:58.7
Heavy Atom Count:11
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes