Prepn process of 4-amino-2-trifluoromethyl benzonitrile

Abstract

The present invention discloses improved process of preparing 4-amino-2-trifluoromethyl benzoitrile. The present invention prepares 4-amino-2-trifluoromethyl benzoitrile with trifluoro methyl fluorobenzene as main material and through three steps of positioning bromination, cyano group replacement and aminolysis substitution. The preparation process uses marketable glacial acetic acid, concentrated sulfuric acid, dibromo hydantoin, cuprous cyanide, liquid ammonia and alcohol, and has less consumption of strong acid and cuprous cyanide. The preparation process has facile materials, simple operation, short path, product purity over 99 % and total product yield up to 73-75 %, less exhaust of harmful matter, and low production cost.

Description

Technical field: [0001] The invention relates to a method for preparing 4-amino-2-trifluoromethylbenzonitrile. technical background: [0002] Bicalutamide is an anti-androgen non-corticosteroid, widely used in the treatment and prevention of prostate cancer, pancreatic cancer, breast cancer and other chronic diseases. Bicalutamide is well tolerated, without any steroidal effect after taking it, and has no obvious side effects on blood vessels and metabolism. Few patients (including the elderly) stop taking the drug because of adverse reactions. The drug was developed and produced by Casodex (Zeneca, UK). It was launched in the UK in 1994, and was subsequently approved for marketing in dozens of countries and regions including the US and China. According to the verification from the State Medical Administration, the administrative protection period of bicalutamide (imported) in my country has expired in October 2005. All domestic pharmaceutical manufacturers can produce bic...

AI Technical Summary

Problems solved by technology

[0004] It can be clearly seen from the above technical route that many raw materials are used in the diazotization step, such as hydrobromic acid, sodium hydroxide, sodium nitrite and other raw materials are required, the operation is cumbersome, there are many by-products, which must be purified, and the adjacent trifluoro The yield of methyl bromide is low, only about 60%

In the iron powder reduction step, the target must be extracted with a solvent. During the extraction process, 4-amino-2-trifluoromethylbenzonitrile is easy to mix with the iron powder, so the extraction is very difficult and must be extracted repeatedly. Need to extract 5 to 6 times, not only need a large amount of solvent, but also affect the color and purity of the target after iron powder reduction, the reaction conditions of the whole preparation process is not easy to control, the yield of the target is only about 30%, the quality is not good Stable, the product color is poor, the production cost is obviously high, and the amount of sewage generated during the preparation process is large, which is not suitable for industrial production

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