Method for preparing 1-fluoronaphthalene

Abstract

The invention provides a method for preparing 1-fluoronaphthalene. The method comprises the following steps of: (1) reacting 1-naphthylamine serving as a raw material and a diazo reagent under acidic conditions to obtain diazonium salt; (2) reacting the diazonium salt obtained in step (1) and fluoroboric acid, phosphorofluoridic acid or salt of the fluoroboric acid and the phosphorofluoridic acid to obtain crude diazonium fluoroborate or crude diazonium fluorophosphate; and (3) replacing and dehydrating the diazonium fluoroborate or the crude diazonium fluorophosphates by using alcohol, replacing the alcohol by using a solvent formed by one or more of methylbenzene, benzene, dimethylbenzene, chlorobenzene, nitrobenzene, chloroform, dichloromethane, dichloroethane, trichloroethylene, cyclohexane and n-hexane, and directly cracking to obtain the 1-fluoronaphthalene. By the method, the technical problem that the diazonium salt is easy to decompose when dried and dehydrated in the traditional process is solved, and the yield and safety of the product are improved; the process is simple, and the industrialization is easy to realize; and the product has high purity and stable characteristics, and fully meets the using requirements when taken as a pharmaceutical intermediate.

Description

technical field [0001] The present invention relates to the technical field of preparation methods of pharmaceutical intermediates, and further relates to the field of preparation methods of 1-fluoronaphthalene, a key intermediate of the antidepressant drug duloxetine. Background technique [0002] In industrialized countries, depression is the most common mental illness, and the lifetime incidence of depression is between 6% and 8%. There are 15 million adults in the United States suffering from depression. With the gradual aging of the population and society, the incidence of depression among people over 60 years old will be as high as 20%-50%. It is predicted that by 2010, the incidence of depression in these countries will increase to about 8%-10%. According to the "2002 World Health Report" published by the World Health Organization, depression has become the fourth largest disease in the world, and by 2020, depression may become the second largest disease after heart ...

AI Technical Summary

Problems solved by technology

These two types of reaction conditions are harsh, difficult to control, high cost, poor safety, and industrial production is difficult to achieve

The third is to use fluorine to replace other halogens for fluorination. This kind of reaction is used in industry, but its application range is limited, and there are many influencing factors, it is difficult to control, and the cost is also high.

There are also many studies on this aspect, but it also has its limitations, especially in the third step of the diazonium salt cracking part, which is cracked after drying as in the traditional method. The diazonium salt begins to crack at about 50 ° C, so It is not advisable to use traditional methods for drying, and it is easy to cause a significant decrease in yield

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