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

Preparation method of (R)-3-amino-4-(2, 4, 5-trifluorophenyl) methyl butyrate

A technology of trifluorophenyl and methyl butyrate, which is applied in the preparation of organic compounds, organic chemical methods, and cyanide reaction preparation, etc., can solve the problems of long reaction route and poor chiral selectivity of products, and achieves easy recovery and application. , good coordination ability, the effect of reducing the cost of use

Active Publication Date: 2021-01-15
江苏八巨药业有限公司
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The present invention aims at the defects existing in the above prior art, provides a kind of preparation method of (R)-3-amino-4-(2,4,5-trifluorophenyl) methyl butyrate, in order to solve the existing The problem of long reaction route and poor chiral selectivity of products

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
  • Preparation method of (R)-3-amino-4-(2, 4, 5-trifluorophenyl) methyl butyrate
  • Preparation method of (R)-3-amino-4-(2, 4, 5-trifluorophenyl) methyl butyrate
  • Preparation method of (R)-3-amino-4-(2, 4, 5-trifluorophenyl) methyl butyrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036]Preparation of 3-amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid methyl ester(Ⅱ)

[0037] Add 80 g of methanol and 20 g of 3-oxo-4-(2,4,5-trifluorophenyl) methyl butyrate to a clean reactor, then stir at room temperature for 10 minutes, then add 25.9 g of Ammonium formate, then, slowly heat up to reflux and keep warm for 5 hours, TLC detection confirms that the reaction is complete, after the reaction, cool down to 50°C and control the temperature not to exceed 50°C, carry out vacuum distillation until no liquid flows out to remove the solvent, and obtain the corresponding concentrate , Then, add 60g of toluene and 30g of water to the concentrate, stir for 30 minutes, leave to stand for layering, collect the organic layer toluene layer, the water layer can be extracted once with 30g toluene, then combine the toluene layer, and add to the collected toluene layer Add 10g of anhydrous sodium sulfate, stir and dry at room temperature for 30 minutes, and filter with suction t...

Embodiment 2

[0046] Preparation of 3-amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid methyl ester(Ⅱ)

[0047] Add 100 g of methanol and 20 g of 3-oxo-4-(2,4,5-trifluorophenyl) methyl butyrate to a clean reactor, then stir at room temperature for 10 minutes, add 23.3 g of formic acid Ammonium, heat up to reflux and keep it warm for 6 hours, TLC detection confirms that the reaction is complete, after the reaction, cool down to 50°C and control the temperature not to exceed 50°C, carry out vacuum distillation until no liquid flows out to remove the solvent, and obtain the corresponding intermediate product concentrate , Then, add 60g of toluene and 30g of water to the concentrate again, stir for 30 minutes, let stand to separate layers, collect the organic layer toluene layer, the water layer can be extracted once with 30g toluene, then merge the collected toluene layer, and pour it into the toluene layer Add 10g of anhydrous sodium sulfate, stir and dry at room temperature for 30 minutes, an...

Embodiment 3

[0056] Preparation of 3-amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid methyl ester(Ⅱ)

[0057] Add 90g of methanol and 20g of 3-oxo-4-(2,4,5-trifluorophenyl) methyl butyrate (I) into a clean reactor, stir at room temperature for 15 minutes, add 24.5g Ammonium formate, then slowly warming up to reflux for 4 hours, TLC detection confirmed the completion of the reaction, after the reaction, cooled to 50 ℃ and under the condition that the temperature was controlled not to exceed 50 ℃, vacuum distillation was carried out until no liquid flowed out to obtain the corresponding Concentrate, then, add 60g toluene and 30g water again in the concentrate, stir 30 minutes, leave standstill layering, collect the organic layer toluene layer, the aqueous layer can be extracted once with 30g toluene, then merge the toluene layer, to the toluene layer collected Add 10g of anhydrous sodium sulfate, stir and dry at room temperature for 30 minutes, and filter with suction to obtain 3-amino-4-(2,...

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 relates to a preparation method of (R)-3-amino-4 (2, 4, 5-trifluorophenyl) methyl butyrate, and belongs to the technical field of drug intermediate synthesis. In order to solve the problems of long route and poor selectivity in the prior art, the invention provides a preparation method of (R)-3-amino-4 (2, 4, 5-trifluorophenyl) methyl butyrate. The preparation method comprises the following steps of: making 3-amino-4 (2, 4, 5-trifluorophenyl) butenedioic acid methyl ester under a reaction under the actions of hydroboron, lewis acid and crown ether to obtain 3-amino-4 (2, 4, 5-trifluorophenyl) methyl butyrate; under the action of an amino alcohol ligand, carrying out a conversion reaction on 3-amino-4-(2, 4, 5-trifluorophenyl) methyl butyrate to synthesize (R)-3-amino-4 (2, 4,5-trifluorophenyl) methyl butyrate. The method can improve the reaction reduction capability, and has the advantages of high catalytic conversion rate, high reaction rate, high yield and high productpurity.

Description

technical field [0001] The invention relates to a preparation method of (R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid methyl ester, belonging to the technical field of pharmaceutical intermediate synthesis. Background technique [0002] Sitagliptin is a dipeptidyl peptidase-Ⅳ (DDP-Ⅳ) inhibitor and a new type of hypoglycemic drug used for the treatment of type Ⅱ diabetes. The drug has a novel mechanism of action that is different from the hypoglycemic drugs currently on the market. It increases insulin secretion and maintains normal blood sugar levels by improving the ability of diabetic patients to produce insulin from their own pancreatic β cells. After taking sitagliptin, it can reduce the activity of DPP-IV to reduce the degradation of incretin, thereby triggering the clinical effect of increasing insulin production by the pancreas and stopping the liver from producing glucose, and finally reducing the blood sugar concentration. [0003] In the process of synthesizin...

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): C07C227/32C07C227/16C07C229/34C07C227/04B01J31/26B01J31/02
CPCC07C227/32C07C227/16C07C227/04B01J31/0271B01J31/0238B01J31/26B01J31/0204B01J27/10B01J27/138B01J27/135C07B2200/07B01J2231/645B01J2231/52B01J35/19C07C229/34
Inventor 汪东海程加铭陈恬程祖福王建军胡建涛
Owner 江苏八巨药业有限公司
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

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com