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Method for preparing lidocaine through continuous reaction

A technology for lidocaine and dimethylaniline, which is applied in the field of continuous reaction preparation of lidocaine, can solve the problems of excessive residue, high cost of raw materials, complicated process operation, etc., and achieves reduction of sewage discharge, reduction of production cost, and simplification of process effect of operation

Active Publication Date: 2020-12-15
山东诚汇双达药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This technical solution mainly has the following defects: (1) In this method, acetone is used as a solvent to prepare lidocaine, and in the next step reaction, diethylamine is reacted, and the solvent cannot be recovered and applied mechanically
(2) Petroleum ether is used for secondary recrystallization in this method, resulting in higher cost of raw materials
(3) In this method, a one-pot method is used to prepare lidocaine, and the yield is only 82%, which is relatively low
(4) There is no process of washing with water to completely remove inorganic salts during the reaction, which will cause the residue to exceed the standard
In this method, there are following defects: (1) the raw materials N,N-diethylaminoacetate methyl ester and 5%Pd / C used as the main catalyst are expensive, and the price of palladium carbon is as high as 40,000 yuan / kg; High cost
(2) Pd / C is the main catalyst, 2,6-dimethylcyclohexanone is the co-catalyst, reacted with ammonia water at high temperature; 185°C for 6 hours, high reaction temperature requires oil bath heating, not suitable for large-scale production
(3) Due to the excessive feeding of N,N-diethylaminoacetate methyl ester, the methanol recovered by distillation cannot be used mechanically; in addition, the total yield is 84~88% low
In this method, the intermediate chloroacetyl-2,6-dimethylaniline needs to be separated, and the process operation is cumbersome, and the expensive and volatile solvent n-hexane is used. The total yield is about 82%, the yield is low, and the cost is high , not suitable for industrial production

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  • Method for preparing lidocaine through continuous reaction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Put 300kg of 2,6-dimethylaniline and 1500kg of ethyl acetate into the reaction kettle, stir; add 307kg of chloroacetyl chloride dropwise, rise to 70-75°C after the dropwise addition, absorb the hydrogen chloride gas produced by deionized water as Dilute hydrochloric acid, apply mechanically to the acid adjustment in the next step; stir the reaction for 1 hour until the reaction is complete, cool down to 50°C, add 520kg of sodium carbonate, 15kg of potassium iodide, and 2400 kg of water, dropwise add 430kg of diethylamine, after the addition is completed, heat up to 70°C until the reaction Complete, cool down to normal temperature; stand still, separate liquid, adjust pH to 3.0-4.0 with dilute hydrochloric acid absorbed by the tail gas before adding the ethyl acetate layer, extract, stand still, separate liquid; recover ethyl acetate from the organic layer; add activated carbon to decolorize and filter the water layer, The filtrate was adjusted to pH=8.0-9.0 with sodium h...

Embodiment 2

[0035] Put 100kg of 2,6-dimethylaniline and 500kg of toluene into the reaction kettle and stir; add 102.5kg of chloroacetyl chloride dropwise, and the addition is completed in about 2 hours; Absorb the hydrogen chloride gas produced as dilute hydrochloric acid, apply mechanically to the next step to adjust the acid; stir the reaction for 1 hour until the reaction is complete, add 175 kg of sodium carbonate, 5 kg of potassium iodide, and 800 kg of water, continue stirring for 0.5 hours to mix uniformly; add 145 kg of diethylamine, Finish adding in about 0.5-1 hour; keep warm for 6-9 hours until the reaction is complete, cool down to room temperature; stand still for 0.5-1 hour; separate liquid, add the dilute hydrochloric acid absorbed by the tail gas before adding the toluene layer to adjust the pH to 2.0-4.5, stir and extract, Stand still for 30 minutes, separate the liquid; recover the solvent toluene from the organic layer; add activated carbon to the water layer to stir and...

Embodiment 3

[0037] Put 300kg of 2,6-dimethylaniline and 1500kg of ethyl acetate into the reaction kettle, stir; start to add 307kg of chloroacetyl chloride dropwise, and the dropwise addition is completed; raise the internal temperature to 70-75°C, and absorb the resulting Hydrogen chloride gas is used as dilute hydrochloric acid, which is applied to the acid adjustment in the next step; stir the reaction for 1 hour until the reaction is complete, cool down to 40-60 ° C, add 515 kg of potassium carbonate, 9 kg of potassium iodide, 2400 kg of water, add 362 kg of diethylamine, and heat up 65 -75°C until the reaction is complete, cool down to room temperature; stand still, separate liquids, add dilute hydrochloric acid absorbed by the tail gas before adding the ethyl acetate layer, adjust the pH to 3.0-3.5, extract, stand still, separate liquids; recover ethyl acetate from the organic layer; water layer Add activated carbon for decolorization and filtration, adjust the pH of the filtrate to ...

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Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing lidocaine through continuous reaction. According to the method, a continuous reaction method is adopted, crystallization, separation, purification and other treatment and drying processes of an intermediate chloroacetyl -2, 6-dimethylaniline are not needed, a lidocaine finished product can be directly obtained, and the molar yield is 93% or above. The process operation is simplified, the solvent is recycled, the sewage discharge amount is reduced, the production cost is reduced, energy conservation and consumption reduction are realized, and the process is green and environment-friendly.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for preparing lidocaine through continuous reaction. Background technique [0002] Lidocaine, chemical name: N-(2,6-xylyl)-2-(diethylamino)acetamide, English name: Lidocaine. Lidocaine is a local anesthetic commonly used in medical clinics. It was used to treat arrhythmia in 1963. It is currently a drug for the prevention and treatment of acute myocardial infarction and various heart diseases complicated by rapid ventricular arrhythmia. Drug of choice for tachycardia and ventricular tremor. [0003] The synthetic method of lidocaine in the prior art mainly contains at present: [0004] Patent CN102070483A discloses a method for preparing lidocaine, which involves a one-pot method for preparing lidocaine. The specific content is: add 305g of 2,6-dimethylaniline to a 5000mL three-necked bottle, and use 2000mL of acetone to prepare Solvent, then ad...

Claims

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Application Information

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IPC IPC(8): C07C237/04C07C231/12C07C231/24
CPCC07C231/12C07C231/02C07C231/24C07C237/04C07C233/07
Inventor 王延斌张健隋海超李跃东黄凤芸任真真
Owner 山东诚汇双达药业有限公司
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