Preparation method of 7-chloro-2-oxoheptanoic acid ethyl ester

A technology of ethyl oxoheptanoate and monoethyl oxalate chloride, applied in the field of preparation of ethyl 7-chloro-2-oxoheptanoate, can solve the problem of low reaction yield, 7-chloro-2-oxo Ethyl heptanoate product has low purity and difficulty in preparing Grignard reagent, so as to achieve the effect of reducing production cost and high yield

Inactive Publication Date: 2014-04-16
太仓浦源医药原料有限公司
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because it is difficult to reach such harsh conditions in industrialized production, and even if the conditions are reached, the occurrence of the Wurtz side reaction cannot be suppressed, resulting in a low reaction yield, and the obtained 7-chloro-2-oxoheptanoic acid ethyl ester The product has a lower purity
[0013] Again, when adopting the Grignard method, the preparation of Grignard reagents is generally carried out in ether solvents, especially in tetrahydrofuran and ether, various Grignard reagents have been successfully prepared, but so far, in benzene solvents especially In toluene, the preparation of Grignard reagent is more difficult

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 method of 7-chloro-2-oxoheptanoic acid ethyl ester
  • Preparation method of 7-chloro-2-oxoheptanoic acid ethyl ester
  • Preparation method of 7-chloro-2-oxoheptanoic acid ethyl ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] According to the preparation method of this example, using 1-bromo-5-chloropentane as the starting material, 7-chloro-2-oxoheptanoic acid ethyl ester was prepared through the following steps:

[0050](1) Add 15g (0.625mol) of magnesium into a 500ml four-neck flask, add 20ml of anhydrous THF and 1ml of 1-bromo-5-chloropentane and stir to initiate the reaction. 100g (0.54mol) of 1-bromo-5-chloropentane was mixed with 400ml of anhydrous THF, and then added dropwise to the four-necked flask. During the dropwise addition, the temperature of the material in the four-necked flask was kept at -10°C to -15°C After dropping, react until the magnesium powder completely disappears to obtain Grignard solution, detect 1-bromo-5-chloropentane residual ≤ 1%, seal it for use;

[0051] (2) In another dry four-neck flask, under mechanical stirring and nitrogen protection, add THF100ml and oxalic acid monoethyl chloride 85g (0.62mol), cool down to -15℃~-10℃, add dropwise 1) For the above-...

Embodiment 2

[0054] According to the preparation method of this example, using 1-bromo-5-chloropentane as the starting material, 7-chloro-2-oxoheptanoic acid ethyl ester was prepared through the following steps:

[0055] (1) Add 24g (1mol) of magnesium into a 500ml four-neck flask, add 20ml of anhydrous THF and 1ml of 1-bromo-5-chloropentane and stir to initiate the reaction. Mix 168g (0.9mol) of 1-bromo-5-chloropentane with 600ml of methyl tetrahydrofuran and add it dropwise into a four-necked flask. During the dropwise addition, the temperature of the material in the four-necked flask is kept at -10°C to -15°C After dropping, react until the magnesium powder completely disappears to obtain Grignard solution, detect 1-bromo-5-chloropentane residual ≤ 1%, seal it for use;

[0056] (2) In a dry 1L four-neck flask, under mechanical stirring and nitrogen protection, add 200ml of methyl tetrahydrofuran and 150g (1.1mol) of monoethyl oxalate chloride, cool down to -10°C ~ -15°C, dropwise add F...

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 discloses a preparation method of 7-chloro-2-oxoheptanoic acid ethyl ester. The method comprises the steps as follows: firstly, 1-bromo-5-chloropentane and magnesium perform a Grignard reaction in a benzene dissolvent containing organic base; secondly, an obtained Grignard solution and ethyloxalylmonochloride perform an addition reaction; lastly, a product obtained from the addition reaction performs an acid hydrolysis reaction to obtain the 7-chloro-2-oxoheptanoic acid ethyl ester. The product, namely the 7-chloro-2-oxoheptanoic acid ethyl ester, obtained via the preparation method disclosed by the invention, has purity over 98 percent, is higher in yield, and remarkably lowers the production cost.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of ethyl 7-chloro-2-oxoheptanoate. Background technique [0002] Ethyl 7-chloro-2-oxoheptanoate is an important starting material for the synthesis of cilastatin. Cilastatin is a renal dehydrodiphthalase inhibitor developed by Merck & Co. of the United States. It can inhibit the renal metabolism of imipenem, a broad-spectrum antimicrobial drug currently in clinical use, and has the effect of reducing nephrotoxicity. At the same time, it can increase the blood inhibitory concentration of imipenem in the body, and the curative effect is very significant. Therefore, in the past ten years, domestic and foreign chemists have carried out a lot of research work on how to improve the purity and yield of synthetic cilastatin. Because ethyl 7-chloro-2-oxoheptanoate is an important starting material for the synthesis of cilastatin, and the purity of the raw m...

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): C07C69/716C07C67/343
CPCC07C67/343C07C67/60
Inventor 周富荣王俊邵林华
Owner 太仓浦源医药原料有限公司
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