Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Method for preparing 3-amino-N-cyclopropyl-2-hydroxyhexanamide

A technology of hydroxycaproamide and cyclopropyl is applied in the field of preparation of pharmaceutical intermediates, which can solve the problems of difficult industrialized operation, harsh reaction conditions, and high raw material prices, and achieves the advantages of cheap and easy-to-obtain raw materials, mild reaction conditions, and simple operation technology. Effect

Inactive Publication Date: 2012-10-03
ZHEJIANG LANGHUA PHARMA
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The raw material L-norvaline used in this route is very expensive, and the second step reaction needs to use Lithium Aluminum Hydride for reduction reaction. The price of this reagent is Very expensive and difficult to operate industrially
The cyclopropyl isocyanate raw material used in the third step reaction is not easy to buy and is not suitable for industrial production
[0011]The raw material trans-2-hexenoic acid used in this route is cheap and easy to get. However, the biggest disadvantage of this route is that it needs to use very expensive Reagents such as HOBT and EDC, and flammable and explosive sodium azide must be used as the ring-opening reagent, the reaction conditions are very harsh, and it is not suitable for large-scale industrial production
In the synthesis method reported in [0012] patent 200710092666.4, the flammable and explosive sodium azide reagent is used, and the reaction conditions are harsh, the operation is inconvenient, and the safety performance is low. Not conducive to industrial production
[0013] The above synthetic methods are not suitable for large-scale production because of the high price of raw materials, harsh reaction conditions, or the use of highly toxic substances

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 3-amino-N-cyclopropyl-2-hydroxyhexanamide
  • Method for preparing 3-amino-N-cyclopropyl-2-hydroxyhexanamide
  • Method for preparing 3-amino-N-cyclopropyl-2-hydroxyhexanamide

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0043] Example 1Add 400g of water in a 1L reaction flask, add trans-2-hexenoic acid (45.7g, 0.4 mol) and cetylpyridinium chloride (13.6g, 0.04 mol) under stirring, and adjust the pH with 30% aqueous sodium hydroxide solution To 6, add 30% hydrogen peroxide (91 g, 0.8 mol) at room temperature, then heat to 50 ° C for 6 hours until the reaction of the raw materials is complete, cool to room temperature, adjust the pH to 2 with concentrated hydrochloric acid, extract twice with 400 g of dichloromethane, and concentrate To dryness, 48.6g was obtained with a yield of 92%.

[0044] In the above implementation, the lye is replaced by ammonia water, sodium carbonate solution, potassium carbonate solution, potassium hydroxide solution, sodium bicarbonate solution or potassium bicarbonate solution, and the catalyst is sodium tungstate or 12-phosphotungstic acid instead of west Pyridium chloride all can obtain above-mentioned same technical effect.

example 2

[0045] Example 2 Add 130g of water into a 1L reaction flask, add trans-2-hexenoic acid (45.7g, 0.4 mol) and sodium tungstate (26.4g, 0.08mol) while stirring, adjust the pH to 5 with aqueous sodium carbonate solution, and 30% hydrogen peroxide (91 g, 0.8 mol) was added. Then heated to 60°C for 5 hours until the reaction of the raw materials was complete, cooled to room temperature, adjusted the pH to 1 with concentrated hydrochloric acid, extracted twice with 400 g of dichloromethane, and concentrated to dryness to obtain 47.5 g with a yield of 90%.

example 3

[0046] Example 3 Add 400g of water in a 1L reaction flask, add trans-2-hexenoic acid (45.7g, 0.4 mol) and cetylpyridinium chloride (20.4g, 0.06 mol) under stirring, and adjust the pH with 30% aqueous sodium hydroxide solution To 6, add 30% hydrogen peroxide (102.3 g, 0.9 mol) at room temperature, then heat to 50 ° C for 5.5 hours until the reaction of raw materials is complete, cool to room temperature, adjust the pH to 2 with concentrated hydrochloric acid, extract twice with 400 g of dichloromethane, Concentrate to dryness to obtain 49.4g, yield 93.5%.

[0047] Preparation of propyl oxirane-2-methyl carboxylate (III)

[0048] Example 4 Add 530g H to a 1L reaction flask 2 O, and started stirring, while adding 3-propyloxirane-2-carboxylic acid (53g, 0.4 mol), adjusted the pH to 8.5 with 30% NaOH aqueous solution, added 265g ethyl acetate, and added Me 2 SO 4 (60.5g, 0.48 mol), the dropwise addition time is about 1 hour, after the addition is complete, continue to rea...

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 3-amino-N-cyclopropyl-2-hydroxyhexanamide, and belongs to the technical field of the preparation of medicinal intermediates. The method comprises the step that 3-amino-N-cyclopropyl-2-hydroxyhexanamide is prepared from trans-2-hexenoic acid by epoxidation, esterification, reduction and other steps. The method has readily-available raw materials and stable process condition, and is suitable for scale industrial production. The 3-amino-N-cyclopropyl-2-hydroxyhexanamide is conveniently prepared from readily-available and low-toxicity raw materials by the step above under a mild reaction condition; the total yield is as high as above 61%, the product has high purity which is as high as above 99.4%; and furthermore, the method achieves high yield and a high-purity product, has a low requirement on the equipment and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of preparation of pharmaceutical intermediates, and in particular relates to a preparation method of 3-amino-N-cyclopropyl-2-hydroxyhexanamide, which has mild reaction conditions, easy-to-obtain raw materials and simple operation, and is suitable for industrial production. Background technique [0002] The amino-N-cyclopropyl-2-hydroxyhexanamide involved in the present invention is an important intermediate for the preparation of antiviral drugs and other pharmaceutical products. For example, the compound can be used to synthesize the anti-hepatitis C drug Telaprevir. [0003] The synthesis method reported in the patent WO2005058821A is as follows: [0004] [0005] The raw material L-norvaline used in this route is very expensive, and the second step reaction needs to use lithium aluminum hydride to carry out the reduction reaction. This reagent is very expensive and difficult to operate industrially....

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): C07C237/06C07C231/02
Inventor 林邦平王忠美郭斌
Owner ZHEJIANG LANGHUA PHARMA
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
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