3-CHLORO-2-FLUORO-5-(TRIFLUOROMETHYL)PYRIDINE

250 ml four-necked round bottom flask equipped with a thermometer, a mechanical stirrer a dropping funnel and an inert gas supply25 ml DMSO was evaporated at 120° C. and 25-30 mbar from a suspension of 150 ml DMSO, 2.5 g potassium carbonate (17.9 mmol) and 25.0 g cesium fluoride (162.9 mmol). The reaction mixture was treated with 25.0 g 2, 3-dichloro-5-trifluoromethylpyridine (12-1, 112.3 mmol) and stirred at 120° C. for 4 h. The suspension was filtered and the product 12-3 was directly distilled out of the distillate at 95 to 115° C. and 40-60 mbar to get 12-3 in quantitative yield. GC analysis: 96.9 area-percent of 12-3.4. Optimized Procedure to Difluoro Trifluoromethyl Pyridine (12-2); The synthesis of the 12-2 was elaborated starting from the corresponding dichloro compound 12-1 or from the very expensive chloro-fluoro compound 12-3. The reactivity of the chloro atom in the 2-position of 12-1 is significant higher compared with the chloro atom in the 3-position. Based on the known safety issue of DMSO in combination with bases like K500mL glass bottle, Supporting serpentine condenser, 54.0 g (0.25 mol) of 2, 3-dichloro-5-trifluoromethylpyridine, DMAC 150g, Anhydrous KF 18.9 g (0.325 mol), 4 g (0.018 mol) of benzyltriethylammonium chloride, The temperature of the oil bath was raised to 170 ° C, Time reaction 5h, After DMAC was recovered by distillation, 2-Fluoro-3-chloro-5-trifluoromethylpyridine was collected under reduced pressure48.6g, Its content of 2-fluoro-3-chloro-5-trifluoromethylpyridine was 99.5percentYield 97percent.Under a nitrogen atmosphere, a 2 L four-necked round bottom flask was charged with 178.7 g (0.827 mol) of2, 3-dichloro-5-trifluoromethylpyridine, 57.6 g (0.992 mol) of anhydrous KFAnd 200 mL of DMSO, The resulting mixture is heated to 115 ° C to 120 ° C and incubated for 3 to 5 hours, cooled to room temperature.Filtered and washed with 40 mL of DMSO to give a DMSO solution of 2-fluoro-3-chloro-5-trifluoromethylpyridine. The fractions were collected by distillation under reduced pressure at 50-55C / 11 mmHg to give a colorless liquid2-Fluoro-3-chloro-5-trifluoromethylpyridine, GC purity of 98.3percent, the yield of 93.6percent.The 1500ml DMSO, 250g 25g of potassium carbonate and cesium fluoride were added to a 5000ml reaction flask was heated in an oil bath, concentrated under reduced pressure to a 500ml DMSO; under nitrogen, was added 250g2, 3--dichloro-5-trifluoromethylpyridine, The reaction at 120 4 hours; distillation under reduced pressure to give a colorless liquid 206g, a yield of 89.2percent.1. In a 200 mL autoclave, add 23.0 g (0.1 mol) of 2, 3, -dichloro-5-trichloromethylpyridine, place a lid on the kettle, and fill it with nitrogen for 1 hour at a pressure of 10.0 MPa for 5 hours to leak the reaction kettle. After confirming that the reactor is leak-free, the pressure in the kettle is vented.The reactor was then placed in an ice-salt bath and cooled when the temperature in the kettle fell below -5°C.The kettle was charged with anhydrous HF 40.0 g (~2.0 mol), and the reaction system was heated to 180°C with stirring, and the reaction was incubated for 12 hours.2. After the reaction is completed, cool down to 25°C, exchange nitrogen in the reactor for half an hour (exchanged gas is passed into 10percent aqueous sodium hydroxide for neutralization absorption), and hydraulically introduce the reaction into a 250 mL round bottom flask. , 70 g (~1.0 mol) of a 25percent aqueous ammonia solution was added and reacted at 35°C for 12 hours under normal pressure.3. After the reaction is complete, collect the oil layer and wash three times until neutral. Add 10g of anhydrous sodium sulfate to the oily liquid and dry it for 6h. Filter the solids out and then conduct vacuum distillation to collect the fraction with a boiling point of 50-55°C/11mmHg.Obtained 16.0 g of 2-fluoro-3-chloro-5-trifluoromethylpyridine product.The content of 2-fluoro-3-chloro-5-trifluoromethylpyridine in the product was determined to be 99.95percent (GC) and the yield was 97.56percent.

Molecular Weight:199.53
XLogP3:2.8
Hydrogen Bond Acceptor Count:5
Exact Mass:198.9811894
Monoisotopic Mass:198.9811894
Topological Polar Surface Area:12.9
Heavy Atom Count:12
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes