Method for preparing 2-amino-4'-fluorobenzophenone

Abstract

The invention discloses a method for preparing 2-amino-4'-fluorobenzophenone. The method comprises the following steps: o-nitrotoluene, trichloroisocyanuric acid, tetramethylpiperidine nitrogen oxideand sodium bromide undergo an oxidation reaction to obtain o-nitrobenzoic acid; the o-nitrobenzoic acid and trichloromethyl carbonate undergo an acylating chlorination to obtain o-nitrobenzoyl chloride; the o-nitrobenzoyl chloride, fluorobenzene and aluminum trichloride undergo a Friedel-Crafts reaction to obtain 2-nitro-4'-fluorobenzophenone; and the 2-nitro-4'-fluorobenzophenone is reduced by hydrogen to the 2-amino-4'-fluorobenzophenone. The method has the advantages of green and environmentally-friendly synthesis route, cheap and easily available initial raw materials, low cost, convenience in operation, suitableness for industrial production, and high yield, and the prepared 2-amino-4'-fluorobenzophenone has a good purity.

Description

technical field [0001] The invention relates to the technical field of chemical substance preparation, in particular to a method for preparing 2-amino-4'-fluoro-benzophenone. Background technique [0002] Pitavastatin calcium is the third-generation statin drug, and it is one of the statin drugs with better blood lipid-lowering effect in international clinical application. It has the characteristics of high efficiency, safety, and good tolerance. 2-Amino-4'-fluoro-benzophenone is a key intermediate used in the production of pitavastatin calcium. [0003] At present, the synthetic routes of 2-amino-4'-fluoro-benzophenone mainly contain the following methods: [0004] Route 1, using o-nitrobenzoic acid as the starting material, the product is obtained through acid chloride reaction, Friedel-Crafts acylation, and reduction. Although the route is relatively short, the acid chloride reaction uses sulfuryl chloride to produce polluting by-products, etc. There are environmental p...

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Problems solved by technology

[0004] Route 1, using o-nitrobenzoic acid as the starting material, the product is obtained through acid chloride reaction, Friedel-Crafts acylation, and reduction. Although the route is relatively short, the acid chloride reaction uses sulfuryl chloride to produce polluting by-products, etc. There are environmental protection problems in the industrial scale-up of this reaction; on the other hand, the raw material cost of this route is relatively high, and it is difficult to realize large-scale industrialization;

[0005] Route 2, using phthalic anhydride as the starting material, first performs Friedel-Crafts acylation reaction with fluorobenzene to obtain p-fluorobenzoylbenzoic acid, and then undergoes acid chloride reaction, amidation reaction, and Hofmann degradation to obtain 2- Amino-4'-fluoro-benzophenone, although the yield of each step of this reaction is high, the reagents used are many and the route is long, which is not conducive to industrial production;

[0006] Route 3, using anisole as a raw material, first protect the amino group with p-toluenesulfonyl chloride, then acyl chloride to obtain acid chloride, and then perform Friedel-Crafts reaction with fluorobenzene to obtain 2-amino-4'-fluoro-benzophenone Ketones, the route is long and the overall yield is low

[0007] It can be seen that the current synthetic route of 2-amino-4'-fluoro-benzophenone is either because of the high cost of raw materials, or because of the long route and complicated operation, or because of the shortcomings of low yield and large environmental pollution. Difficulties in industrialization

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