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

Improved preparation method of Nagelinei

A technology selected from hexamic acid, applied in the preparation of organic compounds, carboxylic acid amide preparation, chemical instruments and methods, etc., can solve the problems of incomplete reaction, difficulty in fully stirring, unsuitable for industrial production, etc.

Inactive Publication Date: 2007-05-30
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] The key step of the process is that the condensation of trans-4-isopropyl-cyclohexylcarbonyl chloride and D-phenylalanine is carried out in the reaction system of acetone-water, and a paste-like colloid is formed during the feeding process, which is difficult to fully Stirring, leading to incomplete reaction
[0016] The above process is not suitable for the needs of industrial production

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
  • Improved preparation method of Nagelinei
  • Improved preparation method of Nagelinei
  • Improved preparation method of Nagelinei

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Embodiment one, the preparation of p-isopropylbenzoic acid (I)

[0086] Put the p-cymene raw material into a 1.0L autoclave and feed oxygen to the internal pressure of 22kg / cm 2 , heated to 105°C under stirring, and maintained under pressure for 2.5 hours. The reaction solution was filtered to remove solids, and the solvent was recovered under reduced pressure; the residue was poured into 500 ml of ice water, and a dark green precipitate appeared after stirring; the solids were collected by filtration and washed with water to obtain 65.0 g of a crude product. Recrystallized with glacial acetic acid-water to obtain 50.5 g of white crystal I, with a melting point of 118-119°C and a yield of 86%. Elemental analysis (C 10 h 12 o 2 =164.20): calculated value C73.15 H7.37; measured value C73.08 H7.37.

Embodiment 2

[0087] The preparation of embodiment two, 4-isopropyl-cyclohexanecarboxylic acid (II)

[0088] In a 1.0-liter autoclave, dissolve 50.0 grams of p-isopropylbenzoic acid in 500 milliliters of glacial acetic acid, then add 10.0 grams of 10% Pd-C, and feed hydrogen to 55.0 kg / cm 2 , heated to 150°C for 8 hours under stirring. After cooling, filter the reaction solution to recover the catalyst; distill the filtrate under reduced pressure to recover acetic acid. The residual oil was distilled at 126°C / 0.7mmHg to obtain 46.1 grams of a colorless transparent viscous liquid, namely 4-isopropyl

[0089] Mixture II of cis-trans isomers of cyclohexanecarboxylic acid, yield 89%.

Embodiment 3

[0090] Embodiment three, the preparation of trans-4-isopropyl cyclohexanecarboxylic acid (III)

[0091] Take 46.0 g of the above mixture II, dissolve it in 150 ml of p-cymene, add 37.0 g of solid potassium hydroxide (content not less than 82%), heat to 145° C. under nitrogen protection, and stir for 6 hours. After the reaction, cool down; add a mixed solution of 60 ml of water and 60 ml of methanol for extraction, separate the lower layer (water / alcohol phase) after standing for stratification, acidify to pH 2 with concentrated hydrochloric acid in an ice bath; stir at low temperature for 1 hour, and filter Precipitate and recrystallize twice with formic acid (content not less than 85%) to obtain 37.0 g of white crystal III, melting point: 94-95°C, yield 80%. The HPLC analysis content was greater than 99%, and no cis-isomer was detected. Elemental analysis (C 10 h 18 o 2 =170.25): calculated value (%) C70.55 H10.66; measured value (%) C70.57 H10.84.

[0092] HPLC instrume...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
Login to View More

Abstract

An improved process for preparing 'Nagelienai' features that the p-isopropylbenzoic acid is reduced by the reducer chosen from active Ni and active Pd or Pd-C to become 4-isopropylcyclohexaformic acid, or the mixture of cis-and anti-4-isopropylcyclohexaformic acids are converted to anti-isopropylcyclohexaformic acid under the action of hydroxide of alkali metal, or the anti-4-isopropylcyclohexacyl chloride reacts on D-phenylpropanoic acid in a mixed solvent system, or the Nagelienai from previous step is recrystallized prification in the mixed organic solvent, and the any two, three, or four of above-said steps are combined.

Description

technical field [0001] The invention relates to an improved preparation method of nateglinide. technical background [0002] The following formula Nateglinide (Nateglinide, chemical name N-(trans-4-isopropylcyclohexyl [0003] [0004] Nateglinide structure [0005] -1-formyl)-D-phenylalanine) is a hypoglycemic drug of the dietary regulator class, which provides an important means for the treatment of type II diabetes by selectively controlling postprandial blood sugar levels. It has the characteristics of quick onset and short drug effect, and is more sensitive to the glucose concentration in the circulatory system, so that the blood sugar level during meals can be controlled more physiologically, and the incidence of hypoglycemia is lower. Good application prospects. [0006] In view of the large dosage of nateglinide, a synthetic process suitable for industrial production must be established. But the preparation method of known each columnine has follow...

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 Patents(China)
IPC IPC(8): C07C233/82C07C231/10A61P3/10
Inventor 仲伯华吴波阎远刘力军陈兰福王亚平
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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