Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

One-pot synthesis method for 5-bromo-2-chloro-4'-ethoxy diphenylmethane

A technology of ethoxydiphenylmethane and a synthesis method, applied in the field of one-pot synthesis of 5-bromo-2-chloro-4'-ethoxydiphenylmethane, can solve the problems of high consumption of Lewis acid, difficulty in solvent recovery, Complex post-processing and other problems, to achieve the effect of good solvent recovery, low production cost and simple operation

Inactive Publication Date: 2014-02-12
苏州中科天马肽工程中心有限公司
View PDF2 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The object of the present invention is to provide a kind of one-pot synthetic method of 5-bromo-2-chloro-4'-ethoxydiphenylmethane, to overcome the post-processing complexity brought by the two-step synthetic route method in the above-mentioned prior art, Excessive consumption of Lewis acid, difficulty in solvent recovery, high production cost, etc.

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] On the 1L four-necked flask, respectively install a mechanical stirrer, a thermometer, a reflux condenser and a constant pressure dropping funnel, under nitrogen protection, first add 100g of 2-chloro-5-bromobenzoic acid (96%, 0.41mol), 400ml di Chloromethane, stirred, and 68.3 g of thionyl chloride (0.58 mol, 1.4 eq) was added dropwise at room temperature for about 10 minutes. Then it was heated to 70° C. and refluxed for 4 hours, and the reaction was stirred; the reaction solvent and excess thionyl chloride were distilled off under reduced pressure. Add fresh 700ml of anhydrous tetrahydrofuran, 56.1g of phenetole (98%, 0.45mol, 1.1eq.) to the bottle, cool down to -5°C in a cooling bath, and slowly add 68.9g of aluminum trichloride (0.52mol, 1.26eq. ), the temperature is controlled to less than 10°C, and the feeding time is 15 minutes. The reaction was kept at 10° C. for 2 hours, and the residual 2-chloro-5-bromobenzoic acid content detected by HPLC was less than 0.5%...

Embodiment 2

[0020] 100g of 2-chloro-5-bromobenzoic acid (96%, 0.41mol), 400ml of dichloromethane were first added to a 1L four-necked flask, stirred, and 68.3g of thionyl chloride (0.58mol, 1.4 eq), about 20 minutes of time for adding. Then it was heated to 70° C. and refluxed for 3 hours, and the reaction was stirred; the reaction solvent and excess thionyl chloride were distilled off under reduced pressure. Add fresh 700ml of anhydrous tetrahydrofuran to the bottle, 51.1g of phenetole (98%, 0.41mol, 1.0eq), cool down to -5°C in a cold bath, and slowly add 65.6g of aluminum trichloride (0.49mol, 1.2eq) , the temperature is controlled to less than 10°C, and the feeding time is about 10 minutes. The reaction was kept at 10° C. for 3 hours, and the residual 2-chloro-5-bromobenzoic acid content detected by HPLC was less than 0.5%, that is, the reaction was stopped.

[0021] The reaction solution was continued to cool to -10°C, and 22.6g of potassium borohydride (98%, 0.41mol, 1.0eq) was ad...

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 one-pot synthesis method for 5-bromo-2-chloro-4'-ethoxy diphenylmethane. The method comprises the following continuous steps of: taking 2-chloro-5-bromobenzoic acid as a raw material, reacting it with thionyl chloride to generate 2-chloro-5-bromobenzoyl chloride, and adding an organic solvent, Lewis acid, phenetole and borohydride to undergo Friedel-Crafts acylation reaction and hydroboration reduction reaction so as to obtain the 5-bromo-2-chloro-4'-ethoxy diphenylmethane. The process involved in the invention has the advantages that the same Lewis acid is used as a catalyst in the Friedel-Crafts acylation reaction and the hydroboration reduction reaction, so that the catalyst consumption is greatly reduced, the operation is simple, and the intermediate needs no separation and purification. By effectively controlling the reaction conditions, and the charging sequence and proportion, the 5-bromo-2-chloro-4'-ethoxy diphenylmethane can be synthesized by one step, and fewer three wastes are discharged, the solvent recovery effect is good, and the production cost is low.

Description

technical field [0001] The invention relates to a one-pot synthesis method of 5-bromo-2-chloro-4'-ethoxydiphenylmethane. Background technique [0002] 5-Bromo-2-chloro-4'-ethoxydiphenylmethane is an important intermediate in the synthesis of the antidiabetic drug Dapagliflozin. It is reported that the synthetic method of 5-bromo-2-chloro-4'-ethoxydiphenylmethane mainly contains the following two kinds: [0003] The synthesis route of 5-bromo-2-chloro-4'-ethoxydiphenylmethane reported in patent WO2010022313 is as follows: starting from 2-chloro-5-bromobenzoic acid, first performing Friedel-Crafts acylation with phenetole to obtain 5 -Bromo-2-chloro-4'-ethoxybenzophenone, and then hydroboration reduction to obtain the product, or use Et 3 Reduction of the carbonyl by SiH and trifluoroacetic acid system affords the product. The two-step reaction of this route uses Lewis acid AlCl at the same time 3 Catalytic, two-step reaction of AlCl 3 Both need to be separated and remove...

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): C07C43/225C07C41/18
CPCC07C41/18C07C45/46C07C51/60
Inventor 孙光福陈昌辉黄俊文刘世领甘立新
Owner 苏州中科天马肽工程中心有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products