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Preparation method of high-purity racemic epinephrine

A technology of adrenaline and racemization, which is applied in the field of medicine, can solve the problems of burden, waste liquid recovery and post-processing cost, etc., and achieve the effects of high recovery rate, cost saving and cost reduction

Active Publication Date: 2018-07-27
AMPHASTAR NANJING PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The salicylaldehyde introduced by this method has caused a burden on downstream purification and detection, and at the same time, the waste liquid recovery and post-treatment costs generated by the 50% acetic acid solution are relatively large

Method used

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  • Preparation method of high-purity racemic epinephrine
  • Preparation method of high-purity racemic epinephrine
  • Preparation method of high-purity racemic epinephrine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Add 10 g of S-epinephrine (e.e.% is 36.8%) and 100 ml of purified water into a 250 ml round bottom flask, start stirring, and adjust the pH to 1.2 with hydrochloric acid. The air in the round bottom flask was replaced with nitrogen. Raise the temperature to 80±5°C. After heat preservation and stirring for 1 hour, cool down to 10±5°C. Add 0.5 g of activated carbon, use nitrogen to replace the air in the round bottom flask, and stir for 30 min. Filter and collect the filtrate. The filtrate was kept at 10±5°C, and the pH was adjusted to 9.0 with ammonia water. The solid was collected by filtration, rinsed with 10 ml of purified water first, and then rinsed with 10 ml of methanol. The solid was collected and dried to obtain 9.24 g of solid, with a weight yield of 92.4%.

[0034] like figure 1 As shown, the retention time (RT) is 4.169min is racemic epinephrine, according to the integral peak area is 12845.69mAU*s, the total peak area is 12845.69mAU*s, the chromatograph...

Embodiment 2

[0039] Add 10 g of S-epinephrine (e.e.% is 36.8%) and 100 ml of purified water into a 250 ml round bottom flask, start stirring, and adjust the pH to 1.0 with hydrochloric acid. The air in the round bottom flask was replaced with nitrogen. Raise the temperature to 80±5°C. After heat preservation and stirring for 1 hour, cool down to 10±5°C. Add 0.5 g of activated carbon, use nitrogen to replace the air in the round bottom flask, and stir for 30 min. Filter and collect the filtrate. The filtrate was kept at 10±5°C, and the pH was adjusted to 9.0 with ammonia water. The solid was collected by filtration, rinsed with 10 ml of purified water first, and then rinsed with 10 ml of methanol. The solid was collected and dried to obtain 9.31 g of solid, with a weight yield of 93.1%. Chromatographic purity 96.3%, e.e.% 0.49%.

Embodiment 3

[0041]Add 10 g of S-epinephrine (e.e.% is 36.8%) and 100 ml of purified water into a 250 ml round bottom flask, start stirring, and adjust the pH to 0.8 with hydrochloric acid. The air in the round bottom flask was replaced with nitrogen. Raise the temperature to 80±5°C. After heat preservation and stirring for 1 hour, cool down to 10±5°C. Add 0.5 g of activated carbon, use nitrogen to replace the air in the round bottom flask, and stir for 30 min. Filter and collect the filtrate. The filtrate was kept at 10±5°C, and the pH was adjusted to 9.0 with ammonia water. The solid was collected by filtration, rinsed with 10 ml of purified water first, and then rinsed with 10 ml of methanol. The solid was collected and dried to obtain 9.15 g of solid, with a weight yield of 91.5%. Chromatographic purity 97.8%, e.e.% 0.32%.

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Abstract

The invention discloses a preparation method of racemic epinephrine represented by the formula 2, wherein the preparation method includes the following steps: directly racemizing a compound 1 in an acidic solution to obtain a compound 2, wherein the acidic solution does not include sodium bisulfite or a salicylic acid racemic agent; specifically, the preparation method includes the steps: (a) in the acidic solution with the pH of 0.5-1.5, making the compound 1 under nitrogen protection, controlling the reaction temperature at 75-95 DEG C, and carrying out a stirring reaction of the compound 1for 1-3 hours; (b) controlling the temperature of the reaction liquid at 5-20 DEG C, adding activated carbon, under nitrogen protection, stirring for 20-40 minutes, filtering, and collecting a filtrate; controlling the filtrate temperature at 5-20 DEG C, adjusting the pH to 8.5-9.5 with ammonia water, after the pH is stable, filtering, washing and drying a filter cake, and thus obtaining a white racemic epinephrine powder with high purity. The weight yield of the product obtained by the preparation method is more than 90%, the chromatographic purity is more than 96%, and the ee value is closeto zero; the cost is saved, the operation is simple, and the preparation method is beneficial to the industrial production and has a broad application prospect.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation method of high-purity racemic epinephrine. Background technique [0002] Adrenaline (Epinephrine, Adrenaline, AD) is a hormone and a neurotransmitter, the main hormone of the adrenal medulla, and its biosynthesis is mainly to form norepinephrine first in the medullary chromium cells, and then further undergo phenethylamine- The role of N-methyltransferase (PNMT) to methylate norepinephrine to form adrenaline. In medicine, adrenaline is used to stimulate the heart when the heart stops, or to dilate the trachea during asthma, to constrict blood vessels of the skin, mucous membranes, and internal organs (such as the kidney), and to dilate coronary arteries and skeletal muscle blood vessels. Because it can directly act on coronary blood vessels to cause vasodilation, improve blood supply to the heart, use its effects of exciting heart contraction of blood vessels and relaxing b...

Claims

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Application Information

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IPC IPC(8): C07C213/10C07C213/00C07C215/60
CPCC07C213/00C07C213/10C07C215/60C07C213/08C07C215/56
Inventor 许驰名王印张傲祥徐勇刚陈松张昊宁
Owner AMPHASTAR NANJING PHARMA
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