Method for preparing 6-methoxy-2-acetonaphthalene

Abstract

The present invention provides a method used for preparing 6-methoxy-2-acetyl naphthalene, and belongs to the field of medicine and chemical industry. The method solves the problems of low yield, high costs, poor safety performance, and so on in the synthetic method of the 6-methoxy-2-acetyl naphthalene. The method comprises the following step: a, acylation: beta-naphthyl methyl ether and acetyl chloride are used as raw materials; Louis acid is used as a catalyst; nitro-paraffin is used as a isomer transposition promoter so as to transfer the acyl in the fifth position into the second position; thus the semi-finished product of the 6-methoxy-2-acetyl naphthalene can be prepared; b, post treatment: the crude product of the 6-methoxy-2-acetyl naphthalene is crystallized again to prepare thefinished product of the 6-methoxy-2-acetyl naphthalene. In the method, the nitro-paraffin is used as the isomer transposition promoter, and has high conversion rate. In addition, the reaction steps are reasonable and simple; the required equipment has low requirements but high security; and the method has less environmental pollution, and is suitable for the industrial production with various scales.

Description

technical field [0001] The invention relates to a method for producing a pharmaceutical intermediate, in particular to a method for producing a pharmaceutical naproxen intermediate 6-methoxy-2-acetylnaphthalene; it belongs to the technical fields of medicine and chemical industry. Background technique [0002] 6-methoxy-2-acetylnaphthalene is an important intermediate of the analgesic and anti-inflammatory drug naproxen (Naproxen). Ethylene dichloride is a solvent, and the acyl group is introduced through acylation reaction with acetyl chloride, but there are more isomer products in the product prepared by this method, which affects the final product 6-methoxyl-2-acetylnaphthalene The yield, in order to make the acyl group substitute on the 2 position, reduce the generation of other isomers, improve the yield of the final product 6-methoxy-2-acetylnaphthalene. The prior art mainly adopts two more practical synthetic methods. [0003] Method 1: first protect the 2-position...

AI Technical Summary

Problems solved by technology

[0002]6-Methoxy-2-acetylnaphthalene is an important intermediate of the analgesic and anti-inflammatory drug Naproxen, and its traditional synthesis method is based on β- Naphthol is raw material, and Lewis acid is catalyst, is solvent with nitrobenzene or ethylene dichloride, introduces acyl group through acylation reaction with acetyl chloride, but there are more isomer products in the product prepared by this method, Thereby affecting the yield of final product 6-methoxy-2-acetylnaphthalene, in order to make acyl substitute on 2 positions, reduce the generation of other isomers, improve the yield of final product 6-methoxyl-2-acetylnaphthalene yield

Although the nitrobenzene used in this method is mainly used as a solvent and partly acts as an isomer transposition accelerator, so that the reaction steps are less, the operation is simple, the corrosion to equipment is lower, and the cost is less, but due to the nitrobenzene The role of benzene isomer transposition promotion is very small, generally it is not used as isomer transposition accelerator, but only as a solvent for the reaction. If nitrobenzene is used as isomer transposition accelerator, the amount added is too small, resulting in The yield and the purity of the final product 6-methoxy-2-acetylnaphthalene are relatively low, the yield is only about 60%, and the purity is only about 95%; Toxic will cause pollution to the environment and poison to the operator's body

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