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

Method for preparing 2-aminothiazol-4-ylacetic acid hydrochloride

A technology of acetic acid hydrochloride and aminothiazole, applied in the field of manufacturing pharmaceutical intermediates, can solve problems such as complicated manufacturing methods, high product cost, unsuitable for industrialization, etc. Handling easy effects

Inactive Publication Date: 2011-01-19
JIANGSU HUAXU PHARMA
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The above-mentioned process is carried out in an organic solvent, and the corresponding product can only be obtained after repeated acid-base treatment. This method has the disadvantages of complicated post-processing and large environmental pollution. Usually, post-processing of the target 2-aminothiazole-4-acetic acid is required. The method of capillary

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
  • Method for preparing 2-aminothiazol-4-ylacetic acid hydrochloride
  • Method for preparing 2-aminothiazol-4-ylacetic acid hydrochloride
  • Method for preparing 2-aminothiazol-4-ylacetic acid hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Suspend 40g of thiourea in 100ml of water, stir for 20 minutes to dissolve and lower the temperature to 0°C, keep the temperature at 0-3°C, drop 68.5ml of ethyl 4-chloroacetoacetate in about 2 hours, after the drop Stir at the same temperature for 3 hours. After the heat preservation is completed, the pH is adjusted to 7 with ammonia water, and white crystals are precipitated, and the intermediate compound of molecular formula 4 is obtained by filtration.

[0033] After cooling 100ml of concentrated hydrochloric acid to 0~3°C, suspend the intermediate compound obtained in the previous step in the prepared cold concentrated hydrochloric acid at this temperature, stir for 60 minutes, then raise the temperature to 60°C, keep it warm for 6 hours, and keep it warm After completion, cool to -5~0°C and filter to obtain 90 g of the target product (chemical formula 1), with a yield of 92% and a purity (HPLC) of 99.5%.

Embodiment 2

[0035] Suspend 60g of thiourea in 160ml of water, stir for 20 minutes to dissolve it and lower the temperature to 0°C, keep the temperature at 1-3°C, drop 132.5ml of ethyl 4-chloroacetoacetate in about 2 hours, after the drop Stir at the same temperature for 3 hours. After the heat preservation is completed, the pH is adjusted to 7 with ammonia water, white crystals are precipitated, and the intermediate compound represented by molecular formula 4 is obtained by filtration.

[0036] After cooling 150ml of concentrated hydrochloric acid to 1-3°C, suspend the intermediate compound obtained in the previous step in the prepared cold concentrated hydrochloric acid at this temperature, stir for 60 minutes, then raise the temperature to 60°C, keep it warm and hydrolyze for 6 hours, After the heat preservation was completed, it was cooled to -3~0°C, and 135.1 g of the target product (chemical formula 1) was obtained by filtration, with a yield of 92% and a purity (HPLC) of 99.6%.

Embodiment 3

[0038] Suspend 100g of thiourea in 250ml of water, stir for 20 minutes to dissolve it and lower the temperature to 0°C, keep the temperature at 0-2°C, drop 171.5ml of ethyl 4-chloroacetoacetate in about 2 hours, after the drop Stir at the same temperature for 3 hours. After the heat preservation is completed, the pH is adjusted to 7 with ammonia water, and white crystals are precipitated, and the intermediate compound of molecular formula 4 is obtained by filtration.

[0039] After cooling 250ml of concentrated hydrochloric acid to 1-2°C, suspend the intermediate compound obtained in the previous step in the prepared cold concentrated hydrochloric acid at this temperature, stir for 60 minutes, then raise the temperature to 60°C, heat-preserve and hydrolyze for 6 hours, and keep warm After completion, cool to -5~-2°C and filter to obtain 228g of the target product (chemical formula 1), with a yield of 92% and a purity (HPLC) of 99.4%.

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 method for preparing 2-aminothiazol-4-ylacetic acid hydrochloride represented by a chemical formula 1. In the method, thiourea and alpha-halo ethyl acetoacetate are used as raw materials to undergo stepwise reaction under an organic solvent condition. The method is characterized by comprising two steps: a first step of reacting 4-chloro ethyl acetoacetate represented by achemical formula 2 with the thiourea represented by a chemical formula 3 in a water phase; and a second step of suspending and reacting white crystals obtained by the first step in cold concentrated hydrochloric acid. The reaction is performed under a more mild condition, and the 2-aminothiazol-4-ylacetic acid hydrochloride, which is a core intermediate of cephalosporin is prepared with high purity and high yield. Meanwhile, the 4-chloro ethyl acetoacetate serving as a starting material can be processed easily at low cost, the solvent used in reaction is water and therefore is safe to the environment. The production cost is thus reduced considerably, which is favorable for industrial development.

Description

technical field [0001] The invention relates to a manufacturing method of a pharmaceutical intermediate, in particular to a manufacturing method of an intermediate 2-aminothiazol-4-ylacetic acid hydrochloride used in the manufacture of cephalosporin antibiotics. Background technique [0002] 7-[2-(2-aminothiazol-4-yl) acetylamino-[3-[[[(N, N)-dimethyl-amino-ethyl-tetrazolium-1- Base]thio]methyl]-8oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid]dihydrochloride (cefotiam hydrochloride) is a compound first disclosed in U.S. Patent No. 4,755,598, which is a cephalosporin antibiotic showing good antibacterial effects on Gram-negative bacteria and Gram-positive bacteria, and is listed in Korean Patent Publication No. 80-1672, No. No. 83-1415 etc. have already disclosed its production method. [0003] [chemical formula 5] [0004] [0005] In the process of manufacturing the compound of chemical formula 5, the manufacture of 2-aminothiazol-4-ylacetic acid hydrochlor...

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): C07D277/40
Inventor 卢标周灏
Owner JIANGSU HUAXU 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