Check patentability & draft patents in minutes with Patsnap Eureka AI!

Method for preparing 4-(2,4,5-trifluorophenyl)-3-oxo-butanoic acid

A technology of trifluorophenyl and oxobutyric acid, which is applied in the preparation of carboxylate/lactone, organic chemistry, etc., can solve the problems of cumbersome operation, complicated reaction process, dangerous raw materials, etc., and achieves high safety and simple steps. , The effect of stable product quality

Inactive Publication Date: 2012-01-18
ZHEJIANG UNIV
View PDF0 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The reaction process of the above preparation method is very complicated, and some raw materials are very dangerous, and the operation is cumbersome

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 preparing 4-(2,4,5-trifluorophenyl)-3-oxo-butanoic acid
  • Method for preparing 4-(2,4,5-trifluorophenyl)-3-oxo-butanoic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] At 25°C, add 50 ml of THF to a 250 ml three-necked flask, add 8.56 g of 2,4,5-trifluorophenylacetonitrile (50 mmol) under stirring, add 6.54 g of activated zinc (100 mmol) after stirring for 10 minutes mol), and continued to stir for 30 minutes. 12.53 g of ethyl α-bromoacetate (75 mmol) was slowly added dropwise to the system, and the dropwise addition was completed, and the stirring was continued for two hours, and the reaction was completed. Add 2.30 g of sodium hydroxide (75 mmol) to the system, stir for half an hour, add 0.5 mol / l dilute hydrochloric acid dropwise until the pH value becomes 4, recrystallize at 0~-10°C, filter and dry, Promptly obtain 8.12 grams of product 4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid (yield is 69.97%, calculate with 2,4,5-trifluorophenylacetonitrile charging amount; Purity is 98.0%). The nuclear magnetic data of the final product obtained is:

[0019] 1 H-NMR (CDCl 3 , 400MHz): 3.32~3.41(t, 2H), 3.71~3.73(t, 2H), 6.52~6.59(m, 1H...

Embodiment 2

[0021] Add 50 ml of THF to a 250 ml three-necked flask at 30°C, add 8.56 g of 2,4,5-trifluorophenylacetonitrile (50 mmol) under stirring, add 5.85 g of activated zinc (90 mmol) after stirring for 10 minutes , continue stirring for 30 minutes. 12.53 g of ethyl α-bromoacetate (75 mmol) was slowly added dropwise to the system, and the dropwise addition was completed, and the stirring was continued for two hours, and the reaction was completed. Add 2.30 g of sodium hydroxide (65 mmol) to the system, stir for half an hour, add 1 mol / l dilute hydrochloric acid dropwise until the pH value becomes 4, recrystallize at 0~-10°C, filter and dry, that is Obtain 8.01 grams of product 4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid (yield is 69.02%, calculate with 2,4,5-trifluorophenylacetonitrile charging amount, purity is 97.0 %), the product nuclear magnetic detection data are with embodiment 1.

Embodiment 3

[0023] Add 50 ml of tetrahydrofuran to a 250 ml three-neck flask at 35°C, add 8.56 g of 2,4,5-trifluorophenylacetonitrile (50 mmol) while stirring, add 6.54 g of activated zinc after stirring for several minutes, and continue stirring. 15.02 g of ethyl α-bromoacetate (90 mmol) was slowly added dropwise to the system, and the dropwise addition was completed, and the stirring was continued for two hours, and the reaction was completed. Add 2.30 grams of sodium hydroxide (75 mmol) to the system, stir for half an hour, add dropwise 1 mol / l of dilute hydrochloric acid until the pH value becomes 5, recrystallize at low temperature, filter and dry to obtain 8.43 grams of product 4 -(2,4,5-trifluorophenyl)-3-oxobutanoic acid (yield is 72.64%, calculated with 2,4,5-trifluorophenylacetonitrile feeding amount; purity is 97.3%) product nuclear magnetic detection Data is with embodiment 1.

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 preparing 4-(2,4,5-trifluorophenyl)-3-oxo-butanoic acid. The method comprises the steps of: (1) adding 2,4,5-trifluorophenyl acetonitrile, ethyl alpha-bromoacetate and zinc to tetrahydrofuran, and reacting to obtain ethyl 4-(2,4,5-trifluorophenyl)-3-oxo-butanoate; and (2) adding a sodium hydroxide solution to the reaction system obtained in the step (1), carrying out a hydrolysis reaction, then adding diluted hydrochloric acid, and post-treating to obtain 4-(2,4,5-trifluorophenyl)-3-oxo-butanoic acid. The preparation method of 4-(2,4,5-trifluorophenyl)-3-oxo-butanoic acid disclosed by the invention has the beneficial effects that: the raw materials are inexpensive and easily available, a large amount of waste acid water is not generated, the yield is relatively high, the product quality is stable, and the method is a process method with industrial prospects.

Description

technical field [0001] The invention belongs to the field of organic synthesis of pharmaceutical intermediates, in particular to a method for preparing 4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid. Background technique [0002] 4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid is an important pharmaceutical and chemical intermediate, especially the key intermediate for the synthesis of Sitagliptin Phosphate, a new drug for treating diabetes. And in the synthesis process of 4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid, according to literature, it is known that 4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid Butyric acid is usually reacted with 1,3,4-trifluorophenylacetic acid and trimethylsilyl malonate carboxyl protecting group. The reaction needs to be reacted with tert-butyllithium at -60°C. The reaction process is as follows: [0003] [0004] The reaction process of the above preparation method is very complicated, and some raw materials are very dangerous, and the operation...

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
IPC IPC(8): C07C59/88C07C51/09
Inventor 杨健段丽君余长泉
Owner ZHEJIANG UNIV
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com