Method for purifying N-(2',6'-xylyl)-2-piperidinecarboxamide type local anesthetic

A technology of piperidine carboxamide and purification method, which is applied in the field of purification of N--2-piperidine carboxamide local anesthetics, can solve the problems of insignificant impurity removal effect, large amount of organic solvent, low yield, etc., and achieve dissolution Small amount, less time-consuming, high yield and high purity

Active Publication Date: 2014-01-22
YICHANG HUMANWELL PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The prior art has the following disadvantages: a large amount of organic solvent is required, and the yield is low; high-temperature dissolution and low-temperature

Method used

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  • Method for purifying N-(2',6'-xylyl)-2-piperidinecarboxamide type local anesthetic
  • Method for purifying N-(2',6'-xylyl)-2-piperidinecarboxamide type local anesthetic
  • Method for purifying N-(2',6'-xylyl)-2-piperidinecarboxamide type local anesthetic

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] 5g levobupivacaine crude product (HPLC purity 96.3%) was added in the mixed solvent of 2ml acetone and 10ml water, polished 1 hour with rubber mill, filtered, dried to obtain 4.8g bupivacaine refined product (yield is 96 %, HPLC purity is 99.21%), and its particle size coefficient is less than 20 μm. Refined product is added in the mixed solvent of 5ml acetone and 5ml ethanol, add hydrochloric acid to form a salt when grinding with rubber mill, polish 1.5 hours, filter, dry to get 3.9g bupivacaine hydrochloride (yield is 72%, HPLC purity is 99.97%), and its particle size coefficient is less than 2 μm.

Embodiment 2

[0053] 5g levobupivacaine crude product (HPLC purity 96.3%) was added in the mixed solvent of 2ml methyl ethyl ketone and 15ml water, polished 2 hours with rubber mill, filtered, dried to obtain 4.6g bupivacaine refined product ( The yield is 92%, the HPLC purity is 99.15%), and its particle size coefficient is less than 15 μ m. Refined product is added in the mixed solvent of 5ml methyl ethyl ketone and 10ml methyl alcohol, adds hydrochloric acid to form salt when grinding with rubber mill, grinds 1.5 hours, filters and dries to get 3.7g bupivacaine hydrochloride (yield is 71% , HPLC purity is 99.95%), and its particle size coefficient is less than 1 μm.

Embodiment 3

[0055] 5g levobupivacaine crude product (HPLC purity 96.3%) was added in the mixed solvent of 2mlDMF and 15ml water, polished 1 hour with rubber mill, filtered, dried to obtain 4.5g bupivacaine refined product (yield is 90% , HPLC purity is 99.36%), and its particle size coefficient is less than 20 μm. Refined product is added in the mixed solvent of 4ml acetone and 8ml ethanol, add hydrochloric acid to form a salt when grinding with rubber mill, polish 1.5 hours, filter, dry to get 3.6g bupivacaine hydrochloride (yield is 71%, HPLC purity is 99.98%), and its particle size coefficient is less than 2 μm.

[0056] Add 54g (S)-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide, 42g potassium carbonate, 150ml N,N-dimethylformamide, 26ml bromopropane into the three-necked flask, The temperature was raised to 83°C, and the reaction was stirred. After the reaction was completed, the reaction mixture was poured into 600 ml of ice water and stirred. After suction filtration, the filter c...

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Abstract

The invention discloses a method for purifying a high-purity N-(2',6'-xylyl)-2-piperidinecarboxamide type local anesthetic. The method comprises the following steps: adding N-(2',6'-xylyl)-2-piperidinecarboxamide type compound bases into a mixed solvent to release most impurities, grinding by using a colloid grinder, filtering, and replacing a small quantity of impurities through using a salifying and emulsifying method to obtain a refined product of which the particle size is smaller than 2 microns. The method is simple to operate and good in repeatability, the purity of the product reaches 99.98%, the final yield reaches 74%, and the particle size coefficient of the product is smaller than 2 microns, so that the method is suitable for large industrial production, has good economic benefits and can significantly improve the production efficiency.

Description

technical field [0001] The invention relates to a method for purifying N-(2',6'-xylyl)-2-piperidinecarboxamide local anesthetics, which improves the purity and belongs to the field of medicine and chemical industry. Background technique [0002] N-(2',6'-xylyl)-2-piperidinecarboxamide local anesthetics such as ropivacaine hydrochloride and bupivacaine are generally used for nerve block anesthesia, local infiltration anesthesia and epidural anesthesia , especially suitable for operations with long local anesthesia, such as obstetrics, hand, foot and rectal surgery. Its mechanism of action is to block the occurrence and conduction of sensory nerve impulses. By directly interacting with voltage-gated sodium ion channels on the nerve membrane, the excitatory valve of nerve fibers is increased, membrane permeability is reduced, and action potentials are prevented. The conduction of nerve impulses, resulting in local anesthesia. [0003] At present, the common purification meth...

Claims

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Application Information

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IPC IPC(8): C07D211/60
CPCC07D211/60
Inventor 严波罗楠宋扬吕金良王孟华符义刚李莉娥郑炜杨家柱
Owner YICHANG HUMANWELL PHARMA
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