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

Penicillin G sulfoxide dimethyl formamide (DMF) composite crystal and preparation method thereof

A technology of composite crystal and penicillin, applied in the field of medicine, can solve the problems of affecting the yield of ring expansion rearrangement reaction, unstable methanol composite crystal, affecting esterification protection reaction, etc., and achieves high stability, simplified solvent system, moisture content and the like. reduced effect

Active Publication Date: 2013-04-24
NORTH CHINA PHARMA COMPANY
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the penicillin G sulfoxide methanol complex crystal contains methanol that can damage the esterification agent and the protective agent, which will affect the progress of the esterification protection reaction, thereby affecting the improvement of the yield of the ring expansion rearrangement reaction, and the methanol of penicillin G sulfoxide The affinity between penicillin G sulfoxide and methanol in the complex crystal is not strong, and it is easily replaced by other organic reagents, that is, the methanol complex crystal of penicillin G sulfoxide is unstable

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
  • Penicillin G sulfoxide dimethyl formamide (DMF) composite crystal and preparation method thereof
  • Penicillin G sulfoxide dimethyl formamide (DMF) composite crystal and preparation method thereof
  • Penicillin G sulfoxide dimethyl formamide (DMF) composite crystal and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] At room temperature, put 30 grams of penicillin G sulfoxide (15% moisture) into a 100ml single-mouth eggplant-shaped bottle, add 12.8ml of DMF, and dissolve in an ultrasonic bath at 35°C to form a DMF mixed solution of penicillin G sulfoxide . The single-mouth eggplant-shaped bottle was cooled, the temperature of the mixed solution was lowered to -10°C and left to stand for 24 hours, filtered to obtain a filter cake, which was washed with 80 ml petroleum ether and dried to obtain 26.6 g of penicillin G sulfoxide DMF composite crystals (molar yield 86.3%).

[0043] The X-ray powder diffraction pattern of the penicillin G sulfoxide DMF composite crystal obtained in Example 1 is shown below. The X-ray powder diffraction pattern is obtained from a copper ray of λ=1.54059 angstrom passing through a monochromator wire filter .

[0044]

[0045] Where d is the interplanar spacing, and A% is the relative strength.

[0046] The melting point of the penicillin G sulfoxide composite c...

Embodiment 2

[0048] At room temperature, put 30 grams of penicillin G sulfoxide (moisture 0.3%) into a 100ml single-mouth eggplant-shaped bottle, add 30ml of DMF (ie N,N-dimethylformamide), and perform in an ultrasonic bath at 30°C Dissolve to obtain a DMF mixed solution of penicillin G sulfoxide. The single-mouth eggplant-shaped bottle was cooled, the temperature of the mixed solution was lowered to -20°C and left for 24h, filtered to obtain a filter cake, washed with 100ml petroleum ether, and dried to obtain 20.5 grams of penicillin G sulfoxide DMF composite crystals (molar yield 56.6 %), the melting point is the heat flow curve measured by a differential scanning calorimeter.

[0049] The melting point of the penicillin G sulfoxide composite crystal obtained in Example 2 measured by a differential scanning calorimeter was: 101.0°C.

Embodiment 3

[0051] At room temperature, put 25 grams of penicillin G sulfoxide (moisture 0.2%) into a 250ml single-mouth eggplant-shaped bottle, add 100ml of the DMF (N,N-dimethylformamide) mother liquor in Example 2 and at 40°C, Dissolve in an ultrasonic bath to form a DMF (N,N-dimethylformamide) mixed solution of penicillin G sulfoxide. The single-mouth eggplant-shaped bottle was cooled, the temperature of the mixed solution was lowered to 5°C and left for 24 hours, filtered to obtain a filter cake, which was washed with 80 ml petroleum ether and dried to obtain 20.3 g of penicillin G sulfoxide DMF composite crystals (molar yield 68.5%).

[0052] The melting point of the penicillin G sulfoxide composite crystal obtained in Example 3 measured by a differential scanning calorimeter is: 101.6°C.

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
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses a penicillin G sulfoxide dimethyl formamide (DMF) composite crystal and a preparation method thereof. The melting point of the composite crystal is not lower than 101 Celsius degrees. The element contents are that 53.6% of carbon (C), 9.9% of nitrogen (N), 22.8% of oxygen (O), 5.9% of hydrogen (H) and 7.55% of sulfur (S). The preparation method is that firstly, the penicillin G sulfoxide is dissolved in the DMF water solution, the water solution containing the DMF or organic solution containing the DMF to obtain the DMF mixed solution of the penicillin G sulfoxide, and then the DMF mixed solution of the penicillin G sulfoxide is cooled and placed quietly, the penicillin G sulfoxide DMF composite crystal is separated out, and the penicillin G sulfoxide DMF composite crystal is filtered, washed and dried. The penicillin G sulfoxide DMF composite crystal is good in stability, low in water content and does not contain impurities to damage protection for the esterification protective reaction. The process of the esterification protective reaction and a ring-enlargement rearrangement reaction is ensured in process of producing cephalosporin alkyl acid. The cephalosporin alkyl acid obtained from the ring-enlargement rearrangement reaction is high in yield and good in quality.

Description

Technical field [0001] The invention relates to the field of medicine, in particular to a penicillin G sulfoxide composite crystal and a preparation method thereof. Background technique [0002] Penicillin G sulfoxide, chemical name (2S,5R,6R)-3,3-dimethyl-6-(2-phenylacetamido)7-oxo-4-thia-1- Azabicyclo[3.2.0]heptane-2-carboxylic acid sulfoxide, molecular formula is C 16 H 18 O 5 N 2 S, the molecular weight is 350.2, and the chemical structure is: [0003] . [0004] Penicillin G sulfoxide is usually obtained by oxidation with penicillin G as the starting material. It is a very important intermediate in the conversion of penicillin G to cephalosporin. It can be synthesized through esterification protection, ring expansion and rearrangement reactions. Various cephalosporan acids (esters), such as 7-ADCA (7-aminodeacetoxycephalosporanic acid), GCLE (7-phenylacetamido-3-chloromethyl-3-cephalosporanic acid p-methoxybenzyl Ester), GCLH (7-phenylacetamido-3-chloromethyl-4-cephalosporan...

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): C07D499/46C07D499/18
Inventor 米振瑞魏青杰段志钢付成名张苗静郑宝丽
Owner NORTH CHINA PHARMA COMPANY
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