3-Chloro-5-(trifluoromethyl)-2-pyridinecarbonitrile

2.745 kg of 3-chloro-2-fluoro-5-trifluoromethylpyridine was dissolved in 49.41 L of acetone, Then, 1.478 kg of 4-dimethylaminopyridine was added thereto, heated under reflux for 5 hours, cooled to 24 ° C, To obtain a reaction solution, and the resulting reaction solution was filtered to obtain a filter cake, The resulting filter cake was vacuum dried at 44 ° C for 1.5 hours to obtain an organic salt; The organic salt obtained in step (1), 0.588 kg of sodium cyanide was added to 8.232 L of chloroform and 1.029 L of water, The reaction was stirred at 20 ° C for 2.5 hours to obtain a mixed solution, and the resulting mixture was allowed to stand at room temperature to obtain an organic phase a;The obtained organic phase a was added to hydrochloric acid to adjust its pH to 3 and then allowed to stand for delamination to obtain an acid water layer and an organic layer, The resulting organic layer was washed with water to pH 6.5 to give washed water and organic phase b; The organic phase b obtained in step was distilled at atmospheric pressure to 60 ° C and then vacuum distilled to collect a vacuum of 2 mmHg, Potassium temperature of 70 ~ 120 fractions that is 3 - chloro - 2 - cyano - 5 - trifluoromethyl pyridine 1.84kg, yield 89percent.Example 4 To the reaction liquid obtained in the above was added 44.6 g (0.910 mol) of NaCN, 13.4 g (0.0415 mol) of TBAB and 200 mL of water, The resulting mixture was heated at 45 ° C to 50 ° C, After stirring for 20-22 hours, water was added and extracted with dichloromethane.The resulting organic layer was concentrated, Distillation gave 127 g of 2-cyano-3-chloro-5-trifluoromethylpyridine as a light yellow liquid, Yield 74.3percent, GC purity 99.33percent.500mL glass bottle, 48.6 g (0.243 mol) of 2-fluoro-3-chloro-5-trifluoromethylpyridine, Dichlorohexane 200g, 40.4 g (0.247 mol) of 30percent sodium cyanide, 4 g (0.018 mol) of benzyltriethylammonium chloride, Warmed to 20 ° C, Timed reaction 10h, After the water treatment, After the oil phase is recovered from dichloroethane, 100-110 ° C / 15 mmHg fractions were collected.46.7 g of a colorless liquid 2-cyano-3-chloro-5-trifluoromethylpyridine was obtained.The content of 2-cyano-3-chloro-5-trifluoromethylpyridine in the product was 99.6percent (GC)The total yield of the two-step reaction is 90.1percent.1.82 kg of 3-chloro-2-chloro-5-trifluoromethylpyridine was dissolved in 27.231 L of methanol, Then 1.0119 kg of triethylamine was added thereto, Heated to reflux for 4 hours, and cooled to 20 ° C to obtain a reaction solution, The resulting reaction solution was filtered to obtain a filter cake, The resulting filter cake was vacuum dried at 40 ° C for 1 hour to obtain an organic salt; The organic salt obtained in step (1), 0.27 kg of hydrocyanic acid was added to 2.7 L of dichloromethane and 1.35 L of water, The reaction was stirred at 0 ° C for 3 hours to obtain a mixed solution, and the resulting mixture was allowed to stand at room temperature to obtain an organic phase a;The obtained organic phase a is added to hydrochloric acid to adjust its pH to 2 and then the layers are separated to obtain an acid water layer and an organic layer, The resulting organic layer was washed with water to a pH of 6 to give the washed water and the organic phase b; The organic phase b obtained in step is distilled at atmospheric pressure to 60 ° C and then distilled under reduced pressure, Collection of vacuum 2mmHg, The temperature of the ketone temperature of 70 to 120 ° C is 1.77 kg of 3-chloro-2-cyano-5-trifluoromethylpyridine, Yield 85.7percent.2.60 kg of 3-chloro-2-bromo-5-trifluoromethylpyridine was dissolved in 65 L of ethanol, Then, 4.47 kg of 4-pyrrolidinylpyridine was added thereto, heated under reflux for 6 hours, cooled to 30 ° C, The resulting reaction solution was filtered and the resulting reaction solution was filtered to obtain a filter cake. The resulting cake was vacuum dried at 50 ° C for 2 hours, Get organic salt; The organic salt obtained in step (1), 0.525 kg of lithium cyanide was added to 7.88 L of dichloroethane and 788 ml of water, The reaction was stirred at 80 ° C for 2 hours to obtain a mixed solution, and the resulting mixture was allowed to stand to separate the organic phase a;The organic phase a was added to hydrochloric acid to adjust its pH to 4 and then allowed to stand for delamination to obtain an acid water layer and an organic layer, The resulting organic layer was washed with water to pH to 7 to give washed water and organic phase b; The organic phase b obtained in step is distilled at atmospheric pressure to 60 ° C and then distilled under reduced pressure, Collection of vacuum 2mmHg, The temperature of the kettle temperature is 70 ~ 120 3-chloro-2-cyano-5-trifluoromethylpyridine (1.82 kg), The yield was 88.1percent.Description 115; 3-Chloro-5-trifluoromethylpvridine-2-carbonitrile; To 3-chloro-2-fluoro-5-trifluoromethylpyridine (10 g, 50 mmol) in DMSO (70 ml) was added potassium cyanide (3.6 g, 55 mmol) over 20 min, ensuring the reaction mixture temperature stayed below 30°C. The reaction mixture was stirred for a further 30 minutes then poured onto ice water (150 ml). The mixture was extracted 3 times with hexane, and the combined organic extracts were evaporated to give a solid (8. 7 g, 84percent). 1H NMR (400 MHz, CDCl3) 8.15 (1 H, d, J 1.2), 8. 88 (1 H, d, J1. O).2, 3-dichloro-5-(trifluoromethyl)pyridine (5.65 mL, 40.5 mmol) was combined with 4-(dimethylamino)pyridine (5.20 g, 42.6 mmol) and propionitrile (65 mL), heated to reflux and agitated overnight. The mixture was cooled to ambient temperature and solution of sodium cyanide (3.00 g, 61.2 mmol) in water (11 mL) was added. After stirring for 5 hours, the reaction was diluted with water (25 mL) and organic phase was separated, washed with water and 2M HCl, dried and evaporated to give the product, 3-chloro-5- (trifluoromethyl)picolinonitrile (6.33 g, 75.7percent yield) as red liquid.Example 3 2.16 kg of 2, 3-dichloro-5-trifluoromethylpyridine was dissolved in 43.2 L of acetone, Then, an activator of 2.46 kg of 4-dimethylaminopyridine was added thereto, heated under reflux for 5 hours, cooled to 25 ° C, The resulting reaction solution was filtered and the resulting reaction solution was filtered to obtain a cake. The resulting cake was vacuum dried at 45 ° C for 1.5 hours to obtain an organic salt; The organic salt obtained in step (1), 0.716 kg of potassium cyanide was added to 8.60 L of dichloromethane and 1.72 L of water, The reaction was stirred at 10 ° C for 2 hours to obtain a mixed solution, and the resulting mixture was allowed to stand at room temperature to obtain an organic phase a;The organic phase a was added to hydrochloric acid to adjust its pH to 4 and then allowed to stand for delamination to obtain an acid water layer and an organic layer, The resulting organic layer was washed with water to a pH of 6 to give the washed water and the organic phase b; The organic phase b obtained in step was distilled at atmospheric pressure to 60 ° C and then distilled under reduced pressure to collect a vacuum of 2 mmHg. The temperature of the kettle temperature was 70-120 ° C was 3-chloro-2-cyano-5-trifluoromethylpyridine 1.88kg, Yield 91percent

Molecular Weight:206.55
XLogP3:2.4
Hydrogen Bond Acceptor Count:5
Exact Mass:205.9858603
Monoisotopic Mass:205.9858603
Topological Polar Surface Area:36.7
Heavy Atom Count:13
Complexity:232
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes