Continuous process for the preparation of (s)-2-acetyloxypropionic acid chloride

一种乙酰氧丙酰氯、乙酰氧基丙酸的技术，应用在制备(S)-2-乙酰氧基丙酰氯的连续领域，能够解决反应效率降低等问题

Inactive Publication Date: 2020-08-18
BRACCO IMAGINIG SPA
View PDF17 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In fact, when water is present in the starting reagents, even in very small amounts, the efficiency of the reaction is greatly reduced
Furthermore, in prior art methods, excess reagents are not recycled in the initial reaction

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
  • Continuous process for the preparation of (s)-2-acetyloxypropionic acid chloride
  • Continuous process for the preparation of (s)-2-acetyloxypropionic acid chloride
  • Continuous process for the preparation of (s)-2-acetyloxypropionic acid chloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Example 1: Preparation of Lactic Acid in Acetic Acid

[0096] A solution of commercially available lactic acid in water (containing 46.5% lactic acid monomer and 3.2% dimer) was fed from the top of an Oldershaw distillation column having a diameter of 5 cm and equipped with 30 orifice plates to the first tray, and metering was started, A stream of acetic acid is fed at its bottom. The flow rates of the two feeds were 1040 and 550 mL / h, respectively. The overhead pressure was 50 Torr and the reflux ratio was 1.

[0097] The distillate flow rate was 550 mL / h. The top product contained only water and traces of acetic acid, while the composition (% by weight) of the product from the bottom of the column was as follows:

[0098] Table 1

[0099] components weight% lactic acid 40.0 Lactic acid dimer 3.9 (S)-2-Acetoxypropionic acid 0.5 (S)-2-Acetoxypropionic acid dimer 0.3 water 2.8 Acetic acid 51.6

Embodiment 2

[0100] Example 2: Acetylation of Lactic Acid

[0101] a. Homogeneous catalysis

[0102] A lactic acid solution in acetic acid, containing 51.1% lactic acid and 5.9% oligomers, with an oligomer / lactic acid ratio equal to 0.11, was fed to a tubular reactor with a volume of 2.6 L and a diameter of 2 cm. The reactor was equipped with a thermostatic jacket. Inside the reactor, the fluid temperature was maintained at 57°C. The solution was fed into the reactor together with a stream of acetic anhydride containing sulfuric acid such that the molar ratio between acetic anhydride and lactic acid was a flow rate of 1.3 / 1. The concentration of sulfuric acid in the reaction mixture was 0.5% by weight. The residence time inside the reactor was 89 minutes, and the obtained conversions (%) are shown in Table 2. The effluent from the reactor was led continuously to an evaporator with a reboiler volume of 2 L, operated at 8 mbar, in which most of the acetic acid was removed by distillati...

Embodiment 3

[0117] Example 3: Chlorination of Acetoxypropionic Acid

[0118] 3.1 Preparation with 3 reactors and a condensing unit

[0119](S)-2-Acetoxypropionic acid, obtained from the bottom of the evaporator described in Example 1, was fed together with thionyl chloride into a continuous stirred reactor with reflux condensation unit and two horizontal tube reactions In a series of reactors (PFR1 and PFR2) formed in series, the reaction gases of which are directed to the condensation unit of the first stirred reactor. The condensate from each condensation unit is completely redirected to the first stirred reactor. The effective volumes of the three reactors are 586, 1380 and 1480 mL respectively, and the total volume is 3446 mL.

[0120] In addition to the acid itself, the acetoxypropionic acid solution contained 2% by weight of acetic acid, 6% by weight of acetylated dimer and about 2% of other products. The feed flow rate of the solution to the first reactor was 524.7 g / h, corres...

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 present invention relates to a continuous method for the preparation of (S)-2-acetyloxypropionic acid from an aqueous solution of lactic acid and acetic anhydride, in acetic acid. (S)-2-acetyloxypropionic acid is used for the preparation of (S)-2-acetyloxypropionic acid chloride, an essential intermediate compound for the preparation of Iopamidol and has to be industrially produced with high purity and suitable quality for producing Iopamidol according to the Pharmacopoeia requirements. The continuous process according to the invention, comprises therefore also the chlorination steps of (S)-2-acetyloxypropionic acid with thionyl chloride to give the corresponding (S)-2-acetyloxypropionic acid chloride which is further distilled to give the suitable purity characteristics for its use for the preparation of non-ionic iodinated contrast agents as Iopamidol.

Description

[0001] This application is a divisional application of a Chinese invention patent application with an application date of December 4, 2013, an application number of 201380065023.4, and an invention title of "Continuous method for preparing (S)-2-acetoxypropionyl chloride". technical field [0002] The invention relates to the preparation of key reagents used in the synthesis of contrast agents of X-ray iodinated compounds. Background technique [0003] Iopamidol (Merck Index, Thirteenth Edition, 2001, No. 5073) (N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[[(2S)-2 -Hydroxy-1-oxypropyl]amino]-2,4,6-triiodo-1,3-benzenedicarboxamide (see formula below) is a widely used contrast agent in diagnostic investigations by X-ray. [0004] [0005] Its synthesis is known since the eighties and is disclosed in GB1472050. Since then, alternative methods for its preparation have been developed, e.g. starting from 5-nitroisophthalic acid, suitably reduced to the corresponding amino der...

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): C07C67/08C07C67/287C07C69/14C07C67/54
CPCC07C67/08C07C67/287C07C69/14Y02P20/582C07C67/313C07C71/00
Inventor S·塞拉吉奥尼P·德卢古A·莫提亚罗A·纳德伊S·斯瓜塞罗R·维拉蒂C·F·威斯卡蒂
Owner BRACCO IMAGINIG SPA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap