Preparation background and overview of 2-amino-4-bromopyridine
2-Amino-4-bromopyridine is a bromoaminopyridine compound. In recent years, people have done a lot of work on the application of bromoaminopyridine. Since the bromine atom/amino group in this type of molecule can continue to be derivatized to introduce other functional groups, it is possible to design and synthesize novel and diverse structures starting from bromoaminopyridine. Heterocyclic compounds are used in the screening and development of innovative medicines or pesticides.
Preparation of 2-amino-4-bromopyridine
Step one: Add ethyl pyruvate into a 20-liter three-necked bottle, cool it to 0 degrees, add hydrogen peroxide dropwise under mechanical stirring, control the temperature during the dripping process to be below 0 degrees, and leave it aside for use after dripping;
Add dichloromethane and the free dichloromethane solution of 4-bromopyridine hydrochloride into a 200-liter reaction kettle (for example, take 5 kg of 4-bromopyridine hydrochloride, dissolve it in 30 liters of water, and add hydrogen carbonate Adjust the pH to 8 with sodium chloride, extract it three times with 50 liters of methylene chloride), ferrous sulfate and a sulfuric acid aqueous solution with a concentration of 50wt%, stir and lower the temperature to minus 10 degrees, and add dropwise the reagent prepared in the 20-liter reaction bottle. The temperature during the dripping process is controlled between minus 10 degrees and 0 degrees polycarbonate. After the dripping, keep warm and stir for one hour. TCL will detect the end of the reaction. Add the reaction system to 100 liters of water, stir thoroughly for 30 minutes, separate the liquids, and repeat this operation. The aqueous phase was colorless cesium bicarbonate, and the organic phase was concentrated to obtain 8.5 kilograms of crude product as brown-red liquid A, which was used directly in the next step without purification.
Second step: Add 8.5 kg of A in batches to 35 liters of ammonia water, stir with methane overnight, and centrifuge to obtain the crude product. Wash with ethyl acetate and centrifuge to obtain 4.5 kg of amide;
Step 3: Add water and sodium hydroxide to the 50-liter reaction kettle, stir and lower the temperature to 0 degrees, add bromine dropwise, cool to minus 10 degrees after dripping, add amide in batches, keep warm and stir for a while hours, and then heated to 80 degrees and reacted for one hour. TCL was detected until the reaction was completed. Then it was lowered to room temperature and centrifuged to obtain a crude product, which was crystallized with toluene to obtain 1.5 kilograms of pure product.
References
[1] Synthesis method of CN201510652275.82-amino-4-bromopyridine
