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With iron; ammonium chloride; In tetrahydrofuran; ethanol; water; for 5h;Reflux;
Preparation Example 7 A mixture of <strong>[136888-21-6]2-chloro-5-fluoro-3-nitropyridine</strong> (4 g), iron powder (6.3 g), ammonium chloride (606 mg), THF (20 mL), water (20 mL) and ethanol (40 mL) was stirred under refluxing with heating for 5 hours. The reaction mixture was cooled to room temperature, the insoluble matter was separated by filtration and the filtrate was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated under reduced pressure to obtain 2-chloro-5-fluoropyridin-3-amine (3.3 g).
11 g
With iron; acetic acid; at 80℃; for 0.5h;
Step A: 2-Chloro-5-fluoropyridin-3-amine. Fe (15.2 g, 272 mmol) was added in portions to a solution of <strong>[136888-21-6]2-chloro-5-fluoro-3-nitropyridine</strong> (12 g, 68 mmol) and HOAc (200 mL). The reaction mixture was stirred at 80 C. for 0.5 hours before cooling to room-temperature and concentrating to dryness under reduced pressure. The residue was suspended in ethyl acetate (100 mL), the resultant suspension filtered through a pad of Celite, and the pad washed with ethyl acetate (20 mL). The filtrate was neutralized with sat. NaHCO3(200 mL) and the resultant mixture extracted with ethyl acetate (3×). These extractions resulted in several fractions which were combined, dried over sodium sulfate and concentrated to dryness under reduced pressure to give the product (11 g), which was used in the next step without further purification. MS (ESI): mass calcd. for C5H4ClFN2 146.0, found 146.8 [M+H]+.
With ethylenediaminetetraacetic acid; dihydrogen peroxide; potassium carbonate; In water; acetonitrile; at 20℃; for 1h;
In 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 30% 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 also1
65 g
With dihydrogen peroxide; In water; acetonitrile; at 20℃; for 1h;
In 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 30% 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 120C. 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.
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