Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method of dextromethorphan

A technology of dextromethorphan and catalyst, which is applied in the field of preparation of dextromethorphan, can solve the problems of high price of trimethylphenyl ammonium hydroxide, increase of production cost of dextromethorphan, and influence on the quality of raw materials, so as to promote economic technology The effect of development, convenient production process and quality improvement

Active Publication Date: 2013-01-30
SUZHOU LIXIN PHARMA
View PDF1 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the high price of trimethylphenylammonium hydroxide and its difficulty in obtaining, the yield of methylation is only about 50%, thus greatly increasing the production cost of dextromethorphan
More prominently, the by-product of this reaction, N,N-dimethylaniline, is a genotoxic substance, and its residual amount will directly affect the quality of the API

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 dextromethorphan
  • Preparation method of dextromethorphan
  • Preparation method of dextromethorphan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] In a 1L three-necked flask, the intermediate II(+)-3-hydroxy-17-methyl-(9α,13α,14α)-morphan (25.7g, 0.1mol), dimethyl carbonate (9.0g, 0.1mol), tetra-n-butylammonium bromide (1.6g, 0.05eq) and toluene 200mL, start stirring, and raise the temperature to 70-75°C until the system is uniformly dissolved. Add solid potassium carbonate (13.8g, 0.1mol) in batches, continue to be warming up to 95 DEG C, keep stirring and reacting under this temperature for 8 hours, TLC detection reaction finishes. Cool down to room temperature, wash the organic phase with dilute hydrochloric acid and water to neutrality, and dry over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was recrystallized from methanol to obtain 19.4 g of off-white solid dextromethorphan (I), with a yield of 71.3%.

Embodiment 2

[0028] In a 1L three-necked flask, the intermediate II(+)-3-hydroxy-17-methyl-(9α,13α,14α)-morphan (25.7g, 0.1mol), dimethyl carbonate (9.0g, 0.1mol), tetra-n-butylammonium bromide (1.6g, 0.05eq), toluene 150mL and water 50mL, start stirring, and heat up to 70-75°C until the system dissolves uniformly. Add solid potassium carbonate (13.8g, 0.1mol) in batches, continue to be warming up to 95 ℃, keep stirring and reacting under this temperature for 6 hours, TLC detection reaction ends. Cool down to room temperature, wash the organic phase with dilute hydrochloric acid and water to neutrality, and dry over anhydrous sodium sulfate. Concentrate under reduced pressure, and recrystallize the residue from methanol to obtain 22.5 g of off-white solid dextromethorphan (I), with a yield of 82.7%.

Embodiment 3

[0030] In a 1L three-necked flask, the intermediate II(+)-3-hydroxy-17-methyl-(9α,13α,14α)-morphan (25.7g, 0.1mol), dimethyl carbonate (9.0g, 0.1mol), trimethylbenzyl ammonium chloride (0.9g, 0.05eq), toluene 150mL and water 50mL, start stirring, and heat up to 70-75°C until the system dissolves uniformly. Add solid potassium carbonate (13.8g, 0.1mol) in batches, continue to be warming up to 95 ℃, keep stirring and reacting under this temperature for 6 hours, TLC detection reaction ends. Cool down to room temperature, wash the organic phase with dilute hydrochloric acid and water to neutrality, and dry over anhydrous sodium sulfate. Concentrate under reduced pressure, and recrystallize the residue from methanol to obtain 23.3 g of off-white solid dextromethorphan (I), with a yield of 85.6%.

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 dextromethorphan (I); and the preparation method comprises the following steps of: selectively carrying out O-methylation on dextromethorphan immediates of (+)-3-hydroxyl-17-methyl-(9 alpha, 13 alpha, 14 alpha)-morphinan (II) and dimethyl carbonate (DMC) under an effect of a catalyst, so as to generate the dextromethorphan (I). The preparation method of the dextromethorphan (I), disclosed by the invention, has the advantages of more convenient product manufacturing process, low cost and higher quality of an obtained product.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis method design and preparation of raw materials and intermediates, and in particular relates to a preparation method of dextromethorphan. Background technique [0002] Dextromethorphan ((+)-3-methoxy-17-methyl-(9α, 13α, 14α)-morphan, I) is the dextroisomer of morphine-like levomorphan methyl ether, which inhibits It is a powerful central antitussive drug whose antitussive strength is equal to or slightly stronger than that of codeine. Due to the low drug resistance and addiction of this variety, it is an antitussive drug suitable for long-term use or high-dose use. The drug has been included in the pharmacopoeia of many countries, and it is also one of the important varieties that my country needs to focus on in this field. [0003] [0004] Dextromethorphan I [0005] There are many reports on the synthetic method of dextromethorphan, most of which are through first synthesizing th...

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): C07D221/28
Inventor 许学农苏健冷秀云张佳生张爱青舒亮
Owner SUZHOU LIXIN PHARMA