Supercharge Your Innovation With Domain-Expert AI Agents!

Low-cost preparation method of calonic acid and calonic anhydride

A caronic acid and acid hydrolysis technology, applied in the preparation of carboxylate/lactone, organic chemistry, etc., can solve the problems of low product yield, poor operation safety, and high raw material price, and achieve specific reaction selectivity and reduce Online concentration, selective and specific effect

Pending Publication Date: 2022-05-10
XINFA PHARMA
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] The synthetic route 4 has a low overall yield, and the price of ethyl diazoacetate used as a raw material is high; its preparation process involves a diazotization reaction, and the operation safety is poor, so it is not suitable for industrial production
[0017] In summary, there are disadvantages such as high raw material price, poor environmental protection, poor operation safety, low product yield, and unfavorable industrialization in the existing preparation methods of karonic anhydride and karonic acid. A safe, low-cost, high-yield and high-purity preparation process that is conducive to industrialization is of great significance for increasing the market supply of carronic anhydride, meeting the production demand of Nirmatrelvir and combating the harm of the new coronavirus

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
  • Low-cost preparation method of calonic acid and calonic anhydride
  • Low-cost preparation method of calonic acid and calonic anhydride
  • Low-cost preparation method of calonic acid and calonic anhydride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] Embodiment 1: the preparation of carronic acid (Ⅵ)

[0087] To a 1000 ml four-neck flask connected with stirring, thermometer, water separator and reflux condenser, add 500 g of toluene, 46.0 g (0.8 mole) of acetone, 99.1 g (1.0 mole) of methyl cyanoacetate (II 1 ), 0.6 gram of piperidine, 0.4 gram of acetic acid, under stirring condition, heat 82-85 ℃ to reflux and separate water for 3 hours; Stir and react at -45°C for 3 hours; after cooling down to room temperature, filter, and transfer the obtained filtrate to a constant pressure dropping funnel for use. In another 2000 ml four-necked flask connected with a stirring and thermometer, add 120 g (0.6 moles) of 27% sodium methoxide methanol solution, keep the inner temperature between 30-35 ° C, and add dropwise to a constant pressure dropping funnel under stirring The filtrate in about 3 hours was added dropwise. Thereafter the reaction was stirred at 35-40°C for 2 hours. Add 300 grams of water, 200 grams of 40% aqu...

Embodiment 2

[0091] Embodiment 2: the preparation of karonic acid (Ⅵ)

[0092] Add 400 g of n-hexane, 30.0 g (0.5 mole) of acetone, 66.0 g (1.0 mole) of malononitrile (II 2 ), 0.6 gram of piperidine, 0.8 gram of benzoic acid, under the condition of stirring, heat 60-65 ℃ to reflux and divide water for 4 hours; Stir and react at 40-45°C for 3 hours; after cooling down to room temperature, filter, and transfer the resulting filtrate to a constant pressure dropping funnel for use. In another 2000 ml four-necked flask connected with a stirring and thermometer, add 120 g (0.6 moles) of 27% sodium methoxide methanol solution, keep the inner temperature between 30-35 ° C, and add dropwise to a constant pressure dropping funnel under stirring The filtrate in about 3 hours was added dropwise. Thereafter the reaction was stirred at 35-40°C for 2 hours. Add 300 grams of water, 200 grams of 40% aqueous sodium hydroxide solution, stir and react at 80-85° C. for 3 hours, and distill out n-hexane and me...

Embodiment 3

[0093] Embodiment 3: the preparation of carronic acid (Ⅵ)

[0094] Add 600 g of ethanol, 30.0 g (0.5 mole) of acetone, 113.0 g (1.0 mole) of ethyl cyanoacetate (II 3 ), 0.6 gram of piperidine, 0.4 gram of acetic acid, under the condition of stirring, heat 75-80 ℃ of reflux with water for 3 hours; Stir and react at -35°C for 3 hours; after cooling down to room temperature, transfer the resulting filtrate to a constant pressure dropping funnel for use. In another 2000 ml four-necked flask connected with a stirring and thermometer, add 200 g of ethanol and 150 g (1.1 moles) of potassium carbonate, keep the internal temperature between 50-55 ° C, and drop them into the constant pressure dropping funnel under stirring The filtrate was added dropwise in about 3 hours. Thereafter the reaction was stirred at 50-55°C for 2 hours. Add 300 grams of water, 200 grams of 40% aqueous sodium hydroxide solution, stir and react at 80-85° C. for 3 hours, and simultaneously distill off ethanol...

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 low-cost preparation method of calonic acid and calonic anhydride. The method comprises the following steps: by taking disubstituted methane (II) and acetone as raw materials, carrying out condensation to obtain 1, 1, 3, 3-tetrasubstituent-2, 2-dimethyl propane, and then carrying out halogenation reaction, cyclization reaction and hydrolysis decarboxylation on the 1, 1, 3, 3-tetrasubstituent-2, 2-dimethyl propane and a halogenation reagent to obtain calonic acid (VI); the obtained calonic acid can be subjected to anhydridation reaction to obtain calonic anhydride. The method provided by the invention has the advantages of cheap and easily available raw materials, safe and simple operation, high reaction selectivity, less side reaction, high product yield and purity, less wastewater generation amount, easy treatment, environmental protection and low cost of calonic anhydride, and is suitable for green industrial production.

Description

technical field [0001] The invention relates to a low-cost preparation method of karonic acid and karonic anhydride, which belongs to the technical fields of fine chemical industry and medicine. Background technique [0002] Caronic anhydride, the chemical name is 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione, is an important pharmaceutical intermediate; it can be used to prepare oral gamma Hepatitis HCV protease inhibitors Boceprevir and Nirmatrelvir, Nirmatrelvir is the main ingredient of Pfizer's new coronavirus treatment drug Paxlovid, and the market demand is large. [0003] Existing reports about the preparation method of karonic anhydride and karonic acid in the prior art, such as: [0004] Chinese patent document CN102070575A adopts methyl isobutenyl ketone as starting material, and (ethoxycarbonylmethyl) dimethyl sulfide ylide ring closure, then utilizes sodium hypochlorite oxidation, acetic anhydride acid anhydride 3-step reaction to obtain carronic anhydride, ...

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): C07C61/04C07C51/09C07D307/93
CPCC07C51/09C07D307/93C07C2601/02C07C61/04
Inventor 李新发戚聿新吴珂周立山刘畅张明峰
Owner XINFA PHARMA
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com