Industrial production method of chloromethyl pyridine derivative

Abstract

The invention discloses an industrial production method of a chloromethyl pyridine derivative. The industrial production method comprises an oxidation reaction process, a nitration reaction process, a replacement reaction process, a rearrangement hydrolysis reaction process and a chloromethylation reaction process. 2,3-dimethyl pyridine as a raw material undergoes an oxidation reaction to produce a pyridine N-oxide, the pyridine N-oxide undergoes a nitration reaction to produce 2,3-dimethyl-4-nitropyridine-N-oxide, the 2,3-dimethyl-4-nitropyridine-N-oxide undergoes a replacement reaction to produce 4-alkoxypyridine-N-oxide, the 4-alkoxypyridine-N-oxide undergoes a rearrangement hydrolysis reaction to produce a 2-hydroxy-4-alkoxypyridine compound, and the 2-hydroxy-4-alkoxypyridine compound undergoes a chloromethylation reaction to produce the refined chloromethyl pyridine compound. The industrial production method realizes recycle of waste produced in production, realizes environmental protection and waste comprehensive utilization, changes waste into values and injurants into benefits, greatly reduces a production cost and improves product competitiveness.

Description

technical field [0001] The invention belongs to the field of organic synthesis chemistry technology, and in particular relates to the production process of chloromethylpyridine derivatives, which are intermediates of prazole drugs. Background technique [0002] Digestive system diseases have always been a type of disease that threatens human health and is difficult to cure. Among them, the incidence of peptic ulcer accounts for 5% of all human beings, and prazoles are currently the most effective drugs for treating peptic ulcers. Therefore, prazoles The drug consistently ranks among the top ten best-selling drugs of the 21st century. This directly leads to a large market demand for its prodrug chloromethylpyridine derivatives. However, there are almost no manufacturers of such intermediates in China, and most of the demand is imported from India. According to the survey, the main reasons for this phenomenon are the long process flow, high production cost, difficulty in han...

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Problems solved by technology

According to the survey, the main reasons for this phenomenon are the long process flow, high production cost, difficulty in handling the "three wastes" produced in the industrial production of this product, serious environmental pollution, and difficulty in recycling, etc.

[0003] Chinese patent application CN102603620A (201210010970) discloses a synthesis method of chloromethylpyridine or its pyridine derivative hydrochloride, but this method is only applicable to pyridine raw materials whose 2nd and 6th positions are both hydrogen

Invention patent CN200910035011.2 discloses a purification method of 2-chloromethyl-4-methoxy-3,5-lutidine hydrochloride, and proposes to use acetone and petroleum ether according to the ratio of 2~3:1 The volume ratio is used as the detergent method of the final product, and the obtained product has good quality and high yield, but there is no specific operation method for other steps

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