Method for synthesizing alecensa hydrochloride intermediate 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid

Abstract

The invention discloses a method for synthesizing an alecensa hydrochloride intermediate 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid. The method is characterized by comprising steps of carrying out Friedel-Crafts reaction on ethylbenzene and 3-halogen-2-methyl-1-propylene to obtain 1-halogn-2-(4-ethyl phenyl)-2-methylpropane; carrying out reaction on the 1-halogn-2-(4-ethyl phenyl)-2-methylpropane and magnesium to obtain 2-(4-ethyl phenyl)-2-methyl propyl magnesium halide; carrying out reaction on the 2-(4-ethyl phenyl)-2-methyl propyl magnesium halide and oxygen to obtain 2-(4-ethyl phenyl)-2-methyl-1-propyl alcohol; oxidizing the 2-(4-ethyl phenyl)-2-methyl-1-propyl alcohol, sodium hypochlorite and sodium chlorite by the aid of 2,2,6,6-tetramethyl piperidine oxide to obtain 2-(4-ethyl phenyl)-2-methylpropanoic acid; carrying out reaction on the 2-(4-ethyl phenyl)-2-methylpropanoic acid and iodine in the presence of oxidizing agents under acidic conditions to obtain the alecensa hydrochloride intermediate. 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid. The 2,2,6,6-tetramethyl piperidine oxide is used as a catalyst. The method has the advantages that the method is easy and convenient to operate, high in yield, low in cost and little in pollution, raw materials for the alecensa hydrochloride intermediate 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid are inexpensive and are easily available, and industrial production can be facilitated.

Description

technical field [0001] The invention belongs to the preparation of organic compounds, and relates to a method for synthesizing alectinib hydrochloride intermediate 2-(4-ethyl-3-iodophenyl)-2-methylpropionic acid. Background technique [0002] Lung cancer is one of the cancers with the highest incidence rate in China, ranking first among male cancer deaths and second among females. Among them, non-small cell lung cancer accounts for 80% of all lung cancers. Once diagnosed, most patients are in the middle and advanced stages of cancer, and the 5-year survival rate is extremely low. At present, the traditional chemotherapy for non-small cell lung cancer is crizotinib, but some patients are not sensitive to crizotinib. Alectinib hydrochloride is still effective for patients who have failed crizotinib chemotherapy. Due to the high incidence of lung cancer and extensive drug resistance, the emergence of alectinib hydrochloride has brought hope to the majority of patients with se...

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Problems solved by technology

[0007] The second is that the application number CN201710118823.8 (publication number CN106946650A) discloses that ethylbenzene is used as a raw material to generate 2-bromo-1-(4-ethylphenyl)-2-methylpropane- 1-ketone, and then catalyzed by anhydrous zinc chloride, aryl migration with trimethyl orthoformate to generate 2-(4-ethylphenyl)-2-methylpropionate methyl ester, and then iodo and hydrolyzed to obtain The target compound; the reaction raw materials have a wide range of sources and are easy to operate, but a large amount of anhydrous aluminum trichloride needs to be used in the reaction process to generate a large amount of acid gas, and a large amount of acid liquid is also required for post-treatment, which is easy to cause corrosion to production equipment and also Bring huge environmental protection pressure; The method reaction process is as follows:

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