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

Preparation of propacetamol hydrochloride

A technology of propadamole hydrochloride and compound, which is applied in the field of preparation of pharmaceutical compounds, can solve problems such as difficult production, harsh reaction conditions, and difficult purification, and achieve an increase in total product yield, mild reaction conditions and easy control, and simple purification operations Effect

Inactive Publication Date: 2009-01-28
ANHUI PIOM PHARMA
View PDF0 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The present invention aims to provide a new method for the large-scale production of proparamole hydrochloride with simple preparation method, low equipment loss and small solvent consumption, aiming at the current difficulties in mass production, harsh reaction conditions and difficult purification.

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 of propacetamol hydrochloride
  • Preparation of propacetamol hydrochloride
  • Preparation of propacetamol hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Embodiment 1: the preparation of chloroacetic acid-4-acetamidophenyl ester

[0019] In a dry and clean 5000ml three-neck round bottom flask, add 604g of paracetamol (4mol), anhydrous potassium carbonate 198g (2mol), tetrahydrofuran 2000ml (24.6mol), ice bath cooling, slowly add chlorine dropwise under stirring Acetyl chloride 304ml (4mol), keep the temperature of the reaction mixture below 10°C. After the dropwise addition was completed, stir at room temperature for 2 hours, and TLC monitored the reaction (developing agent: absolute ethanol: ethyl acetate=10: 10). After the reaction was completed, it was poured into 3000ml of ice water, and a large amount of near-white precipitate was separated out, and was filtered by suction to obtain The white solid was recrystallized from ethanol after drying slightly to obtain 720 g (3.16 mol) of white needle-like solid, with a yield of 79.0%. mp: 185-186.

Embodiment 2

[0020] Embodiment 2: the preparation of N, N'-diethylglycine 4-acetamidophenyl ester

[0021] In a dry and clean 10000ml three-necked round-bottomed flask, add diethylamine (1248ml, 24.96mol) and stir under an ice-water bath, slowly add 720g (3.16mol) chloroacetic acid-4-acetamidophenyl to it in portions And vigorously stirred, the solution was light yellow, after the addition was completed, the reaction was stirred at 15°C for 2 hours, and the reaction was identified by TLC (developing solvent: absolute ethanol: ethyl acetate = 10:5). After the reaction, the excess diethylamine was recovered by concentration under reduced pressure to obtain 740 g (2.8 mol) of light yellow transparent oil, with a yield of 88.6%. Embodiment 3: the preparation of Propatamole Hydrochloride

Embodiment 3

[0022] Add 740g (2.8mol) of N,N'-diethylglycine 4-acetamidophenyl ester, 30ml of ice water and 2000ml of acetone into a 5000ml round bottom flask. 3.5-4.5, filtered with suction to obtain a near white solid, which was recrystallized with an appropriate amount of absolute ethanol after a little drying to obtain 784g (2.6mol) of white needle crystals, yield 92.85%, mp: 227-228°C. One point was identified by TLC (developing solvent: absolute ethanol: sodium carbonate).

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 provides a preparation method of propacetamol hydrochloride. The preparation method is characterized in that chloracetyl chloride and paracetamol carry out an acetylization chloride reaction in a polar aprotic solvent to obtain chloroactic acid-4-acetylamino phenyl ester which is directly aminated with diethylamine to obtain N, N'-diethylglycine 4-acetylamino phenyl ester, hydrochloric acid is used for adjusting the pH to be 4, and the propacetamol hydrochloride is obtained. The preparation method has the advantages of mild condition, convenient separation and purification, the total product yield is greatly increased, the use of the amount of the reaction solvent is low, and the preparation method reduces industrial pollution, and is applicable to industrialized production.

Description

1. Technical field [0001] The invention relates to a preparation method of a pharmaceutical compound, in particular to a preparation method of an antipyretic and analgesic drug, specifically, a preparation method of propatamol hydrochloride. 2. Background technology [0002] Propatamol hydrochloride is a similar derivative drug of acetaminophen (paracetamol) developed abroad in recent years. The drug is developed by USPA (Burma Squibb) and can be administered intramuscularly or intravenously. It passes plasma esters in the blood. The enzyme is rapidly hydrolyzed into acetaminophen, which overcomes the instability of acetaminophen, reduces the toxic and side effects of the original drug, and can replace lysine acetylsalicylic acid (lysaminopirin). Propatamol hydrochloride, as an injectable acetaminophen preparation, solves the problem that acetaminophen is insoluble. According to the literature report on the synthesis method of this drug, Ji Aiguo, Zhao Yanwei and others pub...

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): C07C233/25C07C231/12
Inventor 吴晓明
Owner ANHUI PIOM PHARMA
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