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A kind of preparation method of desvenlafaxine hydrochloride

A technology of venlafaxine hydrochloride and desvenlafaxine, which is applied in the field of pharmaceutical preparation, can solve the problems of complex reaction steps, waste of raw materials, environmental pollution, etc., and achieve good product quality, few by-products, and low temperature. high effect

Active Publication Date: 2016-08-24
JINAN ASIA PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction steps of this method are complicated, and the waste of raw materials is easily caused in the reaction process, and the mercaptan, sodium sulfide, etc. used in the reaction process have relatively strong odors, which easily cause environmental pollution.

Method used

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  • A kind of preparation method of desvenlafaxine hydrochloride
  • A kind of preparation method of desvenlafaxine hydrochloride
  • A kind of preparation method of desvenlafaxine hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Embodiment 1 A kind of preparation method of desvenlafaxine hydrochloride

[0016] Dissolve 5.78kg (18.4mol) of venlafaxine hydrochloride in 19.5L of methanesulfonic acid, add it to a 100L double-layer electric paddle, and add 3.35kg (22.5mol) of methionine. A mixture of desvenlafaxine hydrochloride. The reaction chemical formula is as follows: formula III is venlafaxine hydrochloride; formula IV is desvenlafaxine hydrochloride.

[0017]

[0018] The purification of desvenlafaxine hydrochloride, the steps are as follows:

[0019] (1) Keep the reaction system at 75-80°C and stir for 16 hours, then slowly add 12.5L of water after cooling down to 15-25°C, adjust the pH to 10-12 with 28L of 32% sodium hydroxide solution, and keep the temperature constant When it exceeds 50°C, add 15L of ethyl acetate, stir and mix at 150rpm for 15min, add 0.05kg of activated carbon into the organic phase and stir for 30min, then filter, and distill the solvent under reduced pressure at...

Embodiment 2

[0021] Embodiment 2 A kind of preparation method of desvenlafaxine hydrochloride

[0022] Venlafaxine hydrochloride is dissolved in methanesulfonic acid, and the selected demethylation is methionine; the molar ratio of the addition of methionine to venlafaxine hydrochloride is 1.2:1. The reaction chemical formula is as follows: formula III is venlafaxine hydrochloride; formula IV is desvenlafaxine hydrochloride.

[0023]

[0024] After above-mentioned reaction is finished, the step that carries out purification is as follows:

[0025] (1) Stir the reactant at 75-80°C for 16 hours, then slowly add water after cooling down to 20°C, the volume ratio of the amount of water added to the reaction system is 1.3:2, and the mass fraction is 32% sodium hydroxide Adjust the pH to 11, maintain the temperature at 38°C, add ethyl acetate, stir at a speed of 150r / m for 15min, separate the organic phase and the inorganic phase, the volume ratio of the amount of ethyl acetate added to the ...

Embodiment 3

[0027] Example 3 A preparation method of desvenlafaxine hydrochloride

[0028] Venlafaxine hydrochloride is dissolved in methanesulfonic acid, and the selected demethylation is methionine; the molar ratio of the amount of methionine added to venlafaxine hydrochloride is 1.3:1. The reaction chemical formula is as follows: formula III is venlafaxine hydrochloride; formula IV is desvenlafaxine hydrochloride.

[0029]

[0030] After above-mentioned reaction is finished, the step that carries out purification is as follows:

[0031] (1) Stir the reactant at 75-80°C for 16 hours, then slowly add water after cooling down to 25°C, the volume ratio of the amount of water added to the reaction system is 1.5:2, and the mass fraction is 32% sodium hydroxide Adjust the pH to 10-12, keep the temperature not exceeding 50°C, add ethyl acetate, stir at a speed of 150r / m for 15min, separate the organic phase and the inorganic phase, and add the amount of ethyl acetate to the volume ratio of...

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Abstract

The invention relates to a preparation method of desvenlafaxine hydrochloride. The preparation method comprises the following steps: adding venlafaxine hydrochloride into methanesulfonic acid, and adding a demethylation reagent methionine. The preparation method provided by the invention is green and environment-friendly while the temperature is not high, few byproducts are generated and the product quality is good; and moreover, the yield is over 88%, and the purity reaches 99.9%.

Description

technical field [0001] The invention relates to a preparation method of desvenlafaxine hydrochloride, which belongs to the field of medicine preparation. Background technique [0002] O-desvenlafaxine (ODV), namely desvenlafaxine, the chemical name is 1-[2-(dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclohexanol , the molecular formula is C 16 h 25 NO 2 . ODV (Formula II) is the major metabolite of venlafaxine (Formula I). [0003] [0004] Venlafaxine is demethylated under the conditions of different demethylating reagents and solvents to prepare O-desvenlafaxine. In PCT patent WO2007071404, O-desvenlafaxine is obtained by using metal sulfides, such as sodium sulfide, to demethylate venlafaxine. US20040181093 uses nickel or cobalt to achieve demethylation. In PCT patent WO026453, trialkyl borohydrides are used to achieve demethylation to form an alkali metal salt of desvenlafaxine, which is then neutralized with an acid to obtain desvenlafaxine. Due to the cost of th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C215/64C07C213/00
Inventor 朱富强
Owner JINAN ASIA PHARMA TECH