Preparation method of mepivacaine and optical enantiomer of mepivacaine

A technology of mepivacaine and enantiomers, applied in the field of reaction to obtain mepivacaine or its optical enantiomers, can solve the problems of quaternary ammonium salt by-products, expensive methyl iodide reagents, and high manufacturing costs, and achieve production The effect of low cost, simple operation, and few reaction steps

Active Publication Date: 2013-05-01
SHANDONG CHENGCHUANG BLUE OCEAN PHARM TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Yield is lower 32%, because iodomethane reagent is expensive, and manufacturing cost is higher; Inadequacy also can produce quaternary ammonium salt by-product

Method used

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  • Preparation method of mepivacaine and optical enantiomer of mepivacaine
  • Preparation method of mepivacaine and optical enantiomer of mepivacaine
  • Preparation method of mepivacaine and optical enantiomer of mepivacaine

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Experimental program
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Effect test

Embodiment 1

[0025] Add 46.5 g (0.2 mol) of N-(2,6-dimethylphenyl)-2-piperidine carboxamide and 200 ml of methanol into a 1-liter reaction flask, and control the temperature at 20 ℃ to 25 ℃ to stir and dissolve. Within 10 minutes, add 100ml of 10% sodium hydroxide solution (0.25mol) dropwise and heat to 40 ℃ ~ 45 ℃, add 19.8g (0.22mol) dimethyl carbonate dropwise, and keep the reaction for 4 hours after the dropwise addition. Within hours, the temperature was raised to 65°C, and the reaction was refluxed for 3 hours. Stop the reaction, lower the temperature to 0°C~5°C, add 60ml of concentrated hydrochloric acid, evaporate the solvent under reduced pressure at 40°C, add 100ml of water to dissolve the residue, adjust the pH to 13 with 10% sodium hydroxide at 0°C~5°C, filter , dried in vacuum at 40°C to obtain 47.2 g of mepivacaine. Yield 96.0%. mp 149°C–151°C, MS (EI) C 15 h 22 N 2 O m / z (M +. ): 246.1.

Embodiment 2

[0027] Add 46.5 g (0.2 mol) of N-(2,6-dimethylphenyl)-2-piperidine carboxamide and 200 ml of ethanol to a 1-liter reaction flask, and control the temperature at 20 ℃ to 25 ℃ to stir and dissolve. Within 10 minutes, add 165ml of 10% potassium carbonate solution (0.12mol) dropwise and heat to 40 ℃ ~ 45 ℃, add 19.8g (0.22mol) of dimethyl carbonate dropwise, after the dropwise addition, keep warm for 4 hours, then in 1 hour The temperature was raised to 80°C, and the reaction was refluxed for 5 hours. Stop the reaction, lower the temperature to 0 ℃ ~ 5 ℃, add 60ml of concentrated hydrochloric acid, evaporate the solvent under reduced pressure at 40 ℃, add 100ml of water to dissolve the residue, adjust the pH to 13 with 10% sodium hydroxide at 0 ℃ ~ 5 ℃, filter , and vacuum-dried at 40°C to obtain 35.2 g of mepivacaine. Yield 71.4%.

Embodiment 3

[0029] Add 46.5 g (0.2 mol) of N-(2,6-dimethylphenyl)-2-piperidine carboxamide and 200 ml of ethanol to a 1-liter reaction flask, and stir to dissolve at 20 ℃ to 25 ℃, about Within 10 minutes, add 140ml of 10% potassium hydroxide solution (0.25mol) dropwise and heat to 40 ℃ ~ 45 ℃, add 19.8g (0.22mol) dimethyl carbonate dropwise, and keep the reaction for 4 hours after the dropwise addition. Within hours, the temperature was raised to 80°C, and the reaction was refluxed for 5 hours. Stop the reaction, lower the temperature to 0 ℃ ~ 5 ℃, add 60ml of concentrated hydrochloric acid, evaporate the solvent under reduced pressure at 40 ℃, add 100ml of water to dissolve the residue, adjust the pH to 13 with 10% sodium hydroxide at 0 ℃ ~ 5 ℃, filter , and vacuum-dried at 40°C to obtain 45.5 g of mepivacaine. Yield 92.3%.

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Abstract

The invention discloses a novel preparation method of mepivacaine and an optical enantiomer of the mepivacaine. The method comprises the steps of taking N-(2,6-dimethyl phenyl)-2-piperidinecarboxamide or an optical enantiomer thereof as a starting material, taking dimethyl carbonate as a methylation reagent, stirring at 30-80 DEG C under alkaline catalysis for reaction for 1-10h, and obtaining the mepivacaine or the optical enantiomer thereof. The raw materials adopted by the method are commercially available, extensive and sufficient in source and low in price, reaction conditions of the method are mild, a process is simple, and the disadvantages that hazardous reagents such as dimethyl sulfate and sodium cyanoborohydride are used and anhydrous reaction conditions are required are avoided.

Description

technical field [0001] The present invention relates to a kind of method for preparing mepivacaine and its optical antipodes, and the present invention especially relates to a kind of N-(2,6-dimethylphenyl)-2-piperidine carboxamide or its optical antipodes Enantiomers are used as starting materials, and dimethyl carbonate is used as a methylating reagent to react to obtain mepivacaine or its optical antipodes. Background technique [0002] Mepivaeaine Hydrochloride (Mepivaeaine Hydrochloride), also known as carbocaine hydrochloride, the chemical name is 1-methyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide hydrochloride, It is an amide local anesthetic, its chemical structure is similar to that of lidocaine, but its onset speed is fast, its anesthetic effect is strong, its properties are stable, its toxicity and side effects are small, and when it reaches a certain concentration, it can reduce the impact of cations such as sodium and potassium ions on nerves. The penetrab...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/60
Inventor 姚松芝谢彩霞梁静
Owner SHANDONG CHENGCHUANG BLUE OCEAN PHARM TECH CO LTD
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