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

A technology of methacrylic acid and ethyl phenyl, which is applied in the field of preparation of organic compounds, can solve the problems of environmental protection pressure, production equipment corrosion, etc.

Active Publication Date: 2019-03-08
成都艾必克医药科技有限公司
View PDF5 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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:

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing alecensa hydrochloride intermediate 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid
  • Method for synthesizing alecensa hydrochloride intermediate 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid
  • Method for synthesizing alecensa hydrochloride intermediate 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] The synthetic method of 2-(4-ethyl-3-iodophenyl)-2-methylpropionic acid, the steps are as follows:

[0056] a. Preparation of 1-chloro-2-(4-ethylphenyl)-2-methylpropane (compound 1a):

[0057] At normal temperature, in reactor A with condensing reflux device, add ethylbenzene (159.2g, i.e. 1.5mol), H 2 SO 4 (80%H 2 SO 4 6.13g, or 0.05mol H 2 SO 4 ), stirred evenly, and added 3-chloro-2-methyl-1-propene (90.6g, namely 1.0mol) dropwise with stirring at 40°C. Water, after stirring, let it stand for stratification, remove the lower aqueous phase containing sulfuric acid, leave the organic phase, add an appropriate amount of water and an appropriate amount of saturated sodium chloride aqueous solution to the organic phase again, stir and then let it stand for stratification , discard the lower aqueous phase and saturated aqueous sodium chloride solution; then purify the organic phase by distillation and collect fractions to obtain 1-chloro-2-(4-ethylphenyl)-2-methylpr...

Embodiment 2

[0066] The synthetic method of 2-(4-ethyl-3-iodophenyl)-2-methylpropionic acid, the steps are as follows:

[0067] a. Preparation of 1-chloro-2-(4-ethylphenyl)-2-methylpropane (compound 1a):

[0068] At normal temperature, in reactor A with condensing reflux device, add ethylbenzene (169.9g, i.e. 1.6mol), phosphoric acid (85% phosphoric acid 11.5g, i.e. 0.10mol H 3 PO 4 ), stirred evenly, and added 3-chloro-2-methyl-1-propene (90.6g, namely 1.0mol) dropwise with stirring at 17°C. Water, after stirring, let it stand for stratification, remove the lower aqueous phase containing phosphoric acid, leave the organic phase, add an appropriate amount of water and an appropriate amount of saturated sodium chloride aqueous solution to the organic phase again, stir and let it stand for stratification , discard the lower aqueous phase and saturated aqueous sodium chloride solution; then purify the organic phase by distillation and collect fractions to obtain 1-chloro-2-(4-ethylphenyl)-2...

Embodiment 3

[0077] The synthetic method of 2-(4-ethyl-3-iodophenyl)-2-methylpropionic acid, the steps are as follows:

[0078] a. Preparation of 1-chloro-2-(4-ethylphenyl)-2-methylpropane (compound 1a):

[0079]At room temperature, add ethylbenzene (180.5g, or 1.7mol) and p-toluenesulfonic acid (24.1g, or 0.14mol) to reactor A with a condensing reflux device, stir evenly, and add dropwise at 24°C 3-Chloro-2-methyl-1-propene (90.6g, ie 1.0mol), after the dropwise addition, after the reaction at 36°C for 8 hours, add an appropriate amount of water, stir and let stand, carry out layering, remove The lower part contains the water phase of p-toluenesulfonic acid, leaving the organic phase, adding an appropriate amount of water and an appropriate amount of saturated sodium chloride aqueous solution to the organic phase again, stirring and standing for layering, discarding the lower aqueous phase, saturated Aqueous sodium chloride solution; the organic phase was distilled and purified, and the ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

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...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/363C07C57/58
CPCC07C17/275C07C29/50C07C51/16C07C51/363C07F3/02C07C22/04C07C33/20C07C57/30C07C57/58
Inventor 王新龙宋窈瑶李杰
Owner 成都艾必克医药科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products