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

Method for synthesizing 2 - amido - 9 - capric olefine acid

A technology of optical activity and synthesis method, applied in the synthesis field of optically active 2-amino-9-decenoic acid, can solve the problems of high cost and use price, and achieve the effects of improving synthesis efficiency, reducing cost and shortening synthesis process

Inactive Publication Date: 2007-12-26
上海药明康德新药开发有限公司
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The technical problem to be solved in the present invention is: develop the synthetic technique of practical optically active 2-amino-9-decenoic acid, avoid existing technique to use expensive chiral catalyst or resolution reagent; Shorten the route of existing synthetic technique , increase yield, reduce cost

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 2 - amido - 9 - capric olefine acid
  • Method for synthesizing 2 - amido - 9 - capric olefine acid
  • Method for synthesizing 2 - amido - 9 - capric olefine acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Synthesis of (S)-N-tert-butoxycarbonyl-2-amino-9-decenoic acid

[0021] The first step: the synthesis of (S)-N-tert-butoxycarbonyl-6-oxo-piperidine-2-carboxylic acid ethyl ester

[0022]

[0023] (S)-Ethyl N-tert-butoxycarbonyl-piperidine-2-carboxylate (25.7g, 100mmol) was dissolved in 50mL acetonitrile,

[0024] The catalyst ruthenium chloride (414 mg, 2 mmol) was added. A solution of sodium bromate (22.7 g, 150 mmol) dissolved in 120 mL of water was added dropwise to the above solution over 2 hours. The reaction mixture was stirred at room temperature for 12 h. Add 120 mL of ethyl acetate, separate the water layer, wash the organic layer with 60 mL of 10% sodium thiosulfate aqueous solution, then wash with saturated brine, dry over anhydrous sodium sulfate, filter out the desiccant, and concentrate under reduced pressure to obtain (S)- Ethyl N-tert-butoxycarbonyl-6-oxo-piperidine-2-carboxylate (25 g, 92% yield). 1 HNMR (CDCl 3 ): .1.32(s, 3H), 1.41(s, 9H), 1....

Embodiment 2

[0035] Synthesis of (S)-N-tert-butoxycarbonyl-2-amino-9-decenoic acid ethyl ester

[0036]

[0037]Add p-toluenesulfonyl hydrazide (2.1 g, 0.011 mol) to (S)-N-tert-butoxycarbonyl-2-amino-6-oxo-9-decenoic acid ethyl ester (3.27 g, 0.10 mol) in acetic acid ( 40 mL) solution, stirred at room temperature for one hour, then added sodium borohydride (1.9 g, 0.05 mol) in batches, and continued to stir for 12-24 hours after the addition was complete. After the reaction was detected by TLC, it was quenched by adding water and extracted with ethyl acetate. The organic phases were combined, washed successively with saturated aqueous sodium bicarbonate solution and saturated saline solution, filtered, the filtrate was concentrated under reduced pressure, and the crude product was purified by column chromatography to obtain (S)-N-tert-butoxycarbonyl-2-amino-9-decene Acetate ethyl ester (1.75 g, 56% yield). MS(E / Z): 314(M+H + ).

Embodiment 3

[0039] Synthesis of (R)-N-tert-butoxycarbonyl-2-amino-9-decenoic acid

[0040] Step 1: Synthesis of (R)-N-tert-butoxycarbonyl-2-amino-6-oxo-9-decenoic acid ethyl ester

[0041]

[0042] In the there-necked flask, add magnesium chips (3.5g, 150mmol), a small amount of iodine particles, and heat under a nitrogen stream to get rid of the humid air. After 10 minutes, the system is sealed and protected by nitrogen, and then 1-butyl bromide (35.0g) Anhydrous THF solution (150 mL) was injected into the dropping funnel, and 100 mL of the solution was added at a time, and after the reaction was initiated, it was slowly added dropwise, keeping the reaction temperature between 60-70°C. After the dropwise addition, wait for the temperature of the reaction solution to drop to room temperature, and heat it with a hot air blower for half an hour to make the reaction fully. A solution of (R)-N-tert-butoxycarbonyl-6-oxo-piperidine-2-carboxylic acid ethyl ester (27.1 g, 100 mmol) in anh...

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

This invention relates to a method for preparing optically active 2-amino-9-decenoic acid. The method comprises: attacking chiral 6-oxy-piperidine-2-carboxylate with Grignard reagent of crotyl bromide to obtain chiral 2-amino-6-oxy-9-decadienoate, reducing to convert carbonyl into methylene and obtain chiral or racemized 2-amino-9-decadienoate, and hydrolyzing to obtain optically active 2-amino-9-decenoic acid. The method overcomes the problems of long synthesis route, low yield and expensive chiral catalyst or resolution reagent faced by the present method. The method in this invention has such advantages as simple route, reasonable process, low cost, and high yield, and is suitable for mass production.

Description

Technical field: [0001] The invention relates to a method for synthesizing optically active 2-amino-9-decenoic acid with terminal double bonds. Background technique: [0002] Many protease inhibitors are composed of polypeptides or macrocyclic polypeptides. Optically active long-chain amino acids with terminal double bonds have also appeared in recent years as a component of polypeptides or macrocyclic polypeptides. With the metal metathesis reaction As organic synthesis becomes more and more widely used, such molecules are becoming more and more important in the synthesis of macrocyclic peptides. 2-Amino-9-decenoic acid has been reported in the literature to have good physiological activity. [0003] In current literature reports, there are two methods for the synthesis of chiral 2-amino-9-decenoic acid: the first method is to obtain a A chiral intermediate, the chiral 2-amino-9-decenoic acid can be obtained after removing the prosthetic group (Tetrahedron Lett.1984, 5525...

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): C07C227/22C07C229/30
Inventor 缪伟张治柳马汝建陈曙辉李革
Owner 上海药明康德新药开发有限公司
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