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Preparation method of desvenlafaxine succinate

A technology of desvenlafaxine succinate and desvenlafaxine, applied in carboxylate preparation, carboxylate preparation, chemical instruments and methods, etc., can solve centrifugation difficulties, difficult industrialization, pull through Problems such as low yield

Pending Publication Date: 2022-05-13
CHONGQING ZEN PHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The second step desvenlafaxine forms the highest yield of succinate monohydrate in acetone and water and is 85.8%, and the highest yield of the two-step pull through is 70.8%, and the pull through yield is low; Control at 0-10°C, adjust the pH to 9-10, centrifugation is difficult, and there is filtration, resulting in a large amount of salt remaining in the filter cake of desvenlafaxine, and finally causing the residue on ignition of the raw material drug to be higher than the Pharmacopoeia standard by no more than 0.1 % requirements, not easy for industrialization

Method used

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  • Preparation method of desvenlafaxine succinate

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Embodiment 1

[0029] The preparation of embodiment 1 desvenlafaxine succinate

[0030] Add 89.62kg of venlafaxine, sodium lauryl mercaptide (3.5eq), and N-methylpyrrolidone (3.0ml / g) into the reaction kettle, stir and heat up to 170-180°C, keep stirring and react for 6h, then cool down To below 50°C, add water (5ml / g) and ethyl acetate (4ml / g), control the temperature at 0-10°C, adjust the pH to 1 with concentrated hydrochloric acid, separate the liquids, and use ethyl acetate (4ml / g) for the aqueous phase Wash, control the temperature of the water phase at 20-30°C, add dropwise 40% sodium hydroxide aqueous solution to adjust the pH to 9-10, filter, measure the residue on ignition of the filter cake 2.5%, use purified water 6.8g / g for the filter cake, 20-30°C Beat for 0.5-1.0 hours, centrifuge, filter cake detection residue on ignition 0.06%, get desvenlafaxine wet product, weight 115.33 (kg), water content Wherein, m is the feeding amount of venlafaxine 89.62kg.

[0031] Add desvenlafax...

Embodiment 2

[0032] The preparation of embodiment 2 desvenlafaxine succinate

[0033] Add 85.12kg of venlafaxine, sodium lauryl mercaptide (3.5eq), and N-methylpyrrolidone (3.0ml / g) into the reaction kettle, stir and heat up to 170-180°C, keep stirring and react for 6h, then cool down When the temperature is below 50°C, add water (5ml / g) and ethyl acetate (4ml / g), control the temperature at 0-10°C, adjust the pH to 4 with concentrated hydrochloric acid, separate the liquid, and use dichloromethane (4ml / g) for the aqueous phase Wash, add 40% aqueous sodium hydroxide solution dropwise at 40-50°C to adjust the pH to 9-10 in the water phase, filter, measure the residue on ignition of the filter cake is 2.7%, use purified water 6.8g / g for the filter cake, 20-30°C Beat for 0.5-1.0 hours, centrifuge, filter cake detection residue on ignition 0.05%, get desvenlafaxine wet product, weight 108.11 (kg), water content Wherein, m is the feeding amount of venlafaxine 85.12kg.

[0034] Add desvenlafax...

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Abstract

The invention discloses a high-yield preparation method of a desvenlafaxine succinate bulk drug with firing residues less than 0.1%. The preparation method comprises the following steps: reacting venlafaxine in the presence of a demethylation reagent, acidifying until the pH value is 1.0-4.0, extracting impurities by using an organic solvent, and purifying to obtain the desvenlafaxine succinate. Adjusting the pH value of the system to 9.0-10.0 at 20.0-50.0 DEG C by using alkali, centrifuging, pulping by using water until the burning residue of desmethylvenlafaxine is less than or equal to 0.1%, and salifying the wet product and succinic acid in acetone water. The preparation method disclosed by the invention is high in yield and high in production operability, and large-scale production can be realized.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of desvenlafaxine succinate bulk drug. Background technique [0002] Desvenlafaxine succinate is a new antidepressant drug of the serotonin-norepinephrine reuptake inhibitor class developed by Wyeth Corporation of the United States. The original research company's invention patent CN1501909A discloses the preparation method of desvenlafaxine succinate compound, specifically: adding venlafaxine (55g), dodecyl mercaptan, and ethanol solution of sodium ethoxide into a pressurized container , the temperature was raised to 150° C., and the reaction mixture was stirred for 2 days, then the temperature was lowered and the solution was filtered, and the pH of the filtrate was adjusted to 9.5 with aqueous hydrogen chloride solution, filtered with suction, and the filter cake was washed with ethanol and dried in vacuo to obtain 42 g of free base....

Claims

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Application Information

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IPC IPC(8): C07C213/00C07C213/08C07C213/10C07C215/64C07C51/41C07C51/43C07C55/10
CPCC07C213/00C07C213/08C07C213/10C07C51/412C07C51/43C07C2601/14C07C215/64C07C55/10
Inventor 牟祥谭瑶邓祥林黄治川崔波
Owner CHONGQING ZEN PHARMACEUTICAL CO LTD