Preparation formula of 4'-bromomethyl-2-cyanobiphenyl

Abstract

The invention relates to the technical field of pharmaceutical chemicals, and particularly discloses a preparation formula of 4'-bromomethyl-2-cyanobiphenyl. The 4'-bromomethyl-2-cyanobiphenyl is prepared from, by weight, 550-650 parts of an organic solvent, 550-650 parts of water, 190-195 parts of 4'-methyl-2-cyanobiphenyl, 60-85 parts of bromide, 45-55 parts of bromate or chlorate, 150-250 partsof a hydrochloric acid solution and 450-550 parts of a recrystallization solvent. The formula overcomes the defects of the prior art, and has the advantages of mild reaction conditions, high reactionselectivity, fewer byproducts, low equipment corrosion, simple operation, low cost, low environmental protection pressure, easy product separation, safe and easy operation of bromination reagents, high bromine atom utilization rate, easy industrial production and high product purity.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, in particular to a preparation formula of 4'-bromomethyl-2-cyanobiphenyl. Background technique [0002] Sartan drugs are the first-line antihypertensive drugs, which have a brand-new antihypertensive mechanism, stable antihypertensive effect, good curative effect, long duration of action, and good patient tolerance. Most of the sartan drugs need to be prepared through the intermediate 4'-bromomethyl-2-cyanobiphenyl. The currently disclosed synthetic methods are as follows: [0003] US5621134 describes the preparation of 4'-bromomethyl-2-cyanobiphenyl from inexpensive bromine in the presence of free radical initiating reagents. But this method produces a large amount of by-product hydrogen bromide in the reaction process, and this by-product can suppress the carrying out of bromination reaction, reduces bromination reaction speed, even reaction is incomplete, therefore is ...

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Problems solved by technology

But this method produces a large amount of by-product hydrogen bromide in the reaction process, and this by-product can suppress the carrying out of bromination reaction, reduces bromination reaction speed, even reacts incompletely, therefore is not suitable for commercial production

[0004] CN101200455A discloses that 4'-methyl-2-cyanobiphenyl reacts with a brominating agent to obtain a product under light conditions, but in a large-scale production process, light energy is difficult to introduce into the reactor interior and bottom, which is not suitable for industrial production

Use HBr / NaBrO3, Br2 / NaBrO3 oxidative bromination system respectively, wherein HBr and Br2 belong to highly corrosive and highly toxic high-risk reagents, corrode equipment, and the operation process is unsafe, and the industrial application value of this method is not high

[0007] WO2011073703 oxidizes the bromination system through NaBrO3 / NaHSO3, the amount of NaBrO3 is three times the amount of the substrate, the amount is large, the cost is high, and it is not suitable for commercial production

[0008] In summary, the preparation of 4'-bromomethyl-2-cyanobiphenyl has slow reaction speed, low industrial application value, high production cost, corrosion to equipment, unsafe operation, high cost, and is not suitable for industrial production

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