Process for the preparation of 2-aminomriordan peter dominic ethylpyridines
A technology of haloalkyl and alkoxycarbonyl, which is applied in the field of preparing 2-aminomethylpyridine, and achieves the effect of high yield and easy handling
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Embodiment 1
[0060] Embodiment 1 (method A)
[0061] A mixture of 3-chloro-2-cyano-5-trifluoromethylpyridine (5.1 g) and 5% palladium on charcoal (5.1 mg palladium metal) with methanol and conc. Hydrochloric acid (2.5 mL) was mixed with stirring. After 4 hours, the reaction was judged to be complete by high performance liquid chromatography (hplc). The mixture was filtered through celite, washed with water and methanol, and evaporated to form the hydrochloride salt of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine in 95-97% yield, NMR (at D. 2 O), 4.6 (s, 2H), 8.35 (s, 1H), 8.9 (s, 1H).
Embodiment 2
[0062] Embodiment 2 (method B)
[0063] A solution of potassium cyanide (71.6 g) in water (215 g) was added to 3-chloro-2-fluoro-5-trifluoromethylpyridine (199.5 g) and Aliquat 336 (chloro trioctanoylmethylamine, 12.1 g) in a stirred mixture. Stirring was continued at this temperature for 4 hours until the amount of starting fluoride by hplc was below 1%. The lower organic phase was separated off and washed with aqueous sodium chloride and distilled at 15 mbar at 90°C to give 3-chloro-2-cyano-5-trifluoromethylpyridine (185.8 g, 90% yield) . The product was 98% pure.
Embodiment 3
[0064] Embodiment 3 (method B)
[0065] Add solid sodium cyanide (0.29 g) to a stirred mixture of 3-chloro-2-fluoro-5-trifluoromethylpyridine (0.8 g) and tetrabutylammonium bromide (0.06 g) at 20-25°C , and stirred for 23 hours to give 3-chloro-2-cyano-5-trifluoromethylpyridine (0.68 g, 82% yield by hplc).
[0066] Example of Step (D)
[0067] At 110°C, 2,3-dichloro-5-trifluoromethylpyridine (800 g) was added to a stirred mixture of anhydrous potassium fluoride (320 g) and anhydrous dimethyl sulfoxide, and then at 120° C. Heating for 2 hours and fractional distillation under reduced pressure gave 3-chloro-2-fluoro-5-trifluoromethylpyridine (685 g) in 92% yield (98% purity).
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