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

Preparation method of N-(trans-4-isopropylcyclohexyl-1-formyl)-D-phenylalanine

A technology of phenylalanine and isopropyl ring is applied in the field of preparation of phenylalanine derivative pharmaceutical intermediates and products, and can solve the problems of changing trans configuration, high toxicity of halogenating agents, troublesome post-processing and the like, Achieve the effect of small environmental impact, easy operation and few reaction steps

Inactive Publication Date: 2009-10-21
NANJING UNIV OF TECH
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above methods mainly have the following disadvantages: 1. The reaction steps are longer, which makes the cost higher; 2. Condensing agents and protective agents are used in the reaction, which makes the steps longer and the cost increases. The selected halogenating agent is more toxic , post-processing is more troublesome, and will partially change the trans configuration of the raw material

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 N-(trans-4-isopropylcyclohexyl-1-formyl)-D-phenylalanine
  • Preparation method of N-(trans-4-isopropylcyclohexyl-1-formyl)-D-phenylalanine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Add 6.8g (0.04mol) of trans-4-isopropylcyclohexanecarboxylic acid (IV) into a 150ml three-necked flask, add 60ml of n-hexane, stir and dissolve, then add 11.7g (0.09mol) of oxalyl chloride (V), The reaction was stirred at 25°C, and the hydrogen chloride gas generated was absorbed into a 20% sodium hydroxide solution through a calcium chloride drying tube. The reaction was stirred for about 16 h until almost no bubbles escaped, and the reaction was terminated. After the solvent and excess oxalyl chloride were distilled off by water pump decompression (external temperature<80°C), oil pump vacuum distillation collected 79~81°C / 3mmHg fraction to obtain colorless liquid trans-4-isopropylcyclohexylformyl chloride ( III), weighing 7.7g, yield 95.1%.

[0021] In a 150ml three-necked flask, 3.14g (0.02mol) of D-phenylalanine (II) was dissolved in 35g of a 2% sodium hydroxide solution by mass percentage, and 30ml of acetone was added, cooled in an ice-water bath to maintain the ...

Embodiment 2

[0023] Add 68.1g (0.4mol) of trans-4-isopropylcyclohexanecarboxylic acid (IV) into a 1-liter three-necked flask, add 600ml of n-hexane, stir and dissolve, then add 116.7g (0.92mol) of oxalyl chloride (V) , 50 ° C stirring reaction, the hydrogen chloride gas generated through the calcium chloride drying tube to the mass percent concentration of 20% sodium hydroxide solution to absorb. The reaction was stirred for about 10 h until almost no bubbles escaped, and the reaction was terminated. After the solvent and excess oxalyl chloride were distilled off by water pump decompression (external temperature<80°C), oil pump vacuum distillation collected 79~81°C / 3mmHg fraction to obtain colorless liquid trans-4-isopropylcyclohexylformyl chloride ( III), weight 68.2g, yield 90.3%.

[0024] In a 500ml three-necked flask, 31.4g (0.19mol) of D-phenylalanine (II) was dissolved in 78g of a 10% sodium hydroxide solution by mass percentage, 160ml of acetone was added, cooled in an ice bath, an...

Embodiment 3

[0026]Add 10.2g of trans-4-isopropylcyclohexanecarboxylic acid (IV) into a 150ml three-necked flask, add 100ml of cyclohexane, stir to dissolve, add 34.5g of oxalyl chloride (V), stir and react at 15°C, the resulting The hydrogen chloride gas is absorbed in a 30% sodium hydroxide solution through a calcium chloride drying tube. The reaction was stirred for about 20 h until almost no bubbles escaped, and the reaction was terminated. After the solvent and excess oxalyl chloride were distilled off by water pump decompression (external temperature<80°C), oil pump vacuum distillation collected 79~81°C / 3mmHg fraction to obtain colorless liquid trans-4-isopropylcyclohexylformyl chloride ( III), weighing 7.4g, yield 91.4%.

[0027] In a 150ml three-necked flask, dissolve 9.2g of D-phenylalanine (II) in 21.8g of 20% sodium hydroxide solution by mass percentage, add 110ml of acetone, cool in an ice-water bath, and maintain the temperature at about 0°C . Under vigorous stirring, 8.4 g...

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 N-(trans-4-isopropylcyclohexyl-1-formyl)-D-phenylalanine, which comprises the following steps: step A: trans-4-isopropylcyclohexanecarboxylic acid, halogenating agent and reaction solvent are put into a reactor and stirred to react for 3-25hours when the temperature is controlled at 5-60 DEG C; trans-4-isopropylcyclohexanecarboxylic acyl chloride is obtained by reduced pressure distillation, fraction collection; step B: D-phenylalanine, alkali liquor and reaction solvent are put into a reaction bulb; trans-4-isopropylcyclohexanecarboxylic acyl chloride is added into the reaction bulb to react with the above mixture for 1-15 hours under the stirring state, when the controlling temperature is 0-50 DEG C; water is added for dissolving after the reaction is over, and N-(trans-4-isopropylcyclohexyl-1-formyl)-D-phenylalanine is obtained by filtering after acidification treatment is carried out with acid. The raw materials used in the invention are cheap and easy to be obtained. The method has the advantages of less reaction process, simple reaction condition, convenient operation, mild condition, and high yield and high purity, which is applicable to industrialized production.

Description

Technical field: [0001] The present invention relates to the preparation method of phenylalanine derivative pharmaceutical intermediates and products, especially a kind of N-(trans-4-isopropylcyclohexyl-1-formyl)-D-phenylalanine (Nag Linide) preparation method. Background technique: [0002] Nateglinide is a new type of oral hypoglycemic drug for the treatment of type II diabetes. It was originally jointly developed by Ajinomoto, Yamanouchi and Rousel-Morishifa in Japan. It was launched in Japan in 1999 and was later developed by Novartis. Launched in the US in 2001. It is a new type of non-sulfonylurea oral hypoglycemic drug, which belongs to D-phenylalanine derivatives, acts directly on the -cells, and reduces blood glucose levels by stimulating the secretion of insulin from the pancreas. The extent of insulin release is glucose dependent and the effect disappears at low glucose levels. Clinically, it is mainly used to treat patients with type II diabetes who are ineffe...

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): C07C233/63C07C231/02A61P3/10
Inventor 王德才杨正柏静盖涛李新华欧阳平凯
Owner NANJING UNIV OF TECH
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