Glutamic Acid Benzyl Ester N-Carboxylic Anhydride Crystallization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional methods for producing glutamic acid benzyl ester N-carboxylic anhydride result in crystals with low bulk density and lack storage stability.
Innovation Solution
A method involving dissolving glutamic acid benzyl ester N-carboxylic anhydride in a heated solvent at temperatures above 40°C, followed by adding an anti-solvent like heptane, hexane, or pentane, to precipitate crystals at elevated temperatures, achieving a bulk density of 0.45 g/cm³ or higher and stable crystal polymorphs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional recrystallization methods are used (dissolving in ethyl acetate and adding anti-solvent like carbon tetrachloride or hexane), then purification is achieved, but the bulk density of crystals remains low (0.23-0.38 g/cm³)
Solution Approach 1:
The patent changes the temperature parameter during crystallization, specifically performing crystallization at elevated temperatures (50-80°C) rather than at room temperature or low temperatures. This temperature parameter change results in crystals with bulk density of 0.45 g/cm³ or more, resolving the contradiction between achieving purification and obtaining high bulk density crystals.
2Reliability
If conventional recrystallization methods are used, then purification is achieved, but storage stability of the crystals is insufficient
Solution Approach 1:
The patent changes the temperature parameter to 50-80°C during crystallization, which produces a specific crystal polymorph with superior storage stability. This parameter change ensures both the desired crystal quality and long-term storage stability, resolving the contradiction between manufacturing precision and reliability.
3Manufacturing precision
If crystallization is performed at low temperature (0°C) after adding anti-solvent, then crystals precipitate, but the bulk density remains low and storage stability is poor
Solution Approach 1:
The patent inverts the conventional approach by performing crystallization at high temperature (50-80°C) instead of low temperature (0°C). This inversion of the temperature parameter leads to the formation of crystal polymorphs with high bulk density (0.45 g/cm³ or more) and excellent storage stability, effectively resolving the contradiction between temperature and manufacturing precision.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method produces crystal polymorphs with enhanced storage stability and bulk density, as demonstrated by powder X-ray diffraction patterns and bulk density measurements.
Implementation Method 1
dissolving glutamic acid benzyl ester N-carboxylic anhydride in a solvent which has been heated at a temperature equal to or higher than 40°C
Implementation Method 2
adding an anti-solvent... to precipitate crystals at elevated temperatures
Implementation Method 3
cooling the crystals
Data Source
Figure 1~2
Figure 3~4
Figure 5
AI summary
An object of the present invention is to provide crystal polymorphs which have a high bulk density and are excellent in storage stability, among crystal polymorphs of a glutamic acid benzyl ester N-carboxylic anhydride. According to the present invention, the crystal polymorphs of glutamic acid benzyl ester N-carboxylic anhydride that have a bulk density of 0.45 g/ cm3 or higher can be obtained by dissolving glutamic acid benzyl ester N-carboxylic anhydride in a solvent which has been heated at a temperature equal to or higher than 40°C and lower than a boiling point thereof and is in an amount of 0.5 L or more per mol of the glutamic acid benzyl ester N-carboxylic anhydride, adding a poor solvent which is in an amount of 1.4 L or more per mol of the glutamic acid benzyl ester N-carboxylic anhydride at a temperature equal to or higher than 40°C and lower than a boiling point thereof, precipitating crystals at a temperature equal to or higher than 40°C and lower than a boiling point thereof, and cooling the crystals.