CN111943910A - Dioxopropazine hydrochloride and preparation method thereof - Google Patents
Dioxopropazine hydrochloride and preparation method thereof Download PDFInfo
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Abstract
The invention provides dioxopromethazine hydrochloride and a preparation method thereof, wherein the preparation method comprises the following steps: (1) and (3) oxidation reaction: the solution A contains free promethazine, and a potassium hydrogen persulfate solution is dripped into the solution A at low temperature to oxidize the promethazine into dioxopromethazine to obtain a solution B; (2) salt forming reaction: dissociating the dioxopromethazine in the solution B into dichloromethane by using sodium hydroxide, washing an organic phase with water, removing a solvent, dissolving the organic phase after the solvent is removed by using acetone, and introducing hydrogen chloride gas into the acetone to prepare a dioxopromethazine hydrochloride crude product; (3) and (3) refining reaction: dissociating the crude dioxopromethazine hydrochloride into dioxopromethazine base by using sodium hydroxide, dissolving in acetone, decolorizing with activated carbon, vacuum filtering, and introducing hydrogen chloride gas into acetone to obtain a refined dioxopromethazine hydrochloride. The method adopts the potassium hydrogen persulfate as the oxidant, has simple and safe operation, low requirement on equipment, no need of pressurization, low energy consumption, high yield of the dioxopromethazine hydrochloride and high purity.
Description
Technical Field
The invention relates to the technical field of organic synthesis of dioxopromethazine hydrochloride, in particular to dioxopromethazine hydrochloride and a preparation method thereof.
Background
The dioxopromethazine hydrochloride has strong antitussive effect, and has effects of resisting histamine, relieving smooth muscle spasm, resisting inflammation and local anesthesia. The existing method for preparing dioxopromethazine hydrochloride mostly adopts a hydrogen peroxide oxidation system, needs heating or reflux, belongs to a dangerous chemical process, and has high safety risk, high requirement on equipment and complex preparation steps.
CN106749098B discloses a method for preparing dioxopromethazine hydrochloride by using oxygen as an oxidant, which comprises the steps of taking promethazine hydrochloride as a substrate, carrying out alkaline hydrolysis to obtain promethazine, and preparing dioxopromethazine hydrochloride by using oxygen as an oxidant and palladium acetate as a catalyst, wherein the total yield is over 90.0%, and the content of dioxopromethazine hydrochloride is more than or equal to 98.8%. The preparation method adopts palladium acetate as a catalyst, is expensive, is not easy to recycle, improves the production cost, is easy to cause palladium poisoning, thereby leading the palladium acetate to lose activity and influencing the oxidation effect, and in addition, adopts oxygen as an oxidant, has longer reaction time and increases the cost of equipment.
Disclosure of Invention
The invention provides dioxopromethazine hydrochloride and a preparation method thereof, wherein potassium hydrogen persulfate is used as an oxidant, the operation is simple and safe, the requirement on equipment is not high, pressurization is not required, the energy consumption is low, the yield of dioxopromethazine hydrochloride is high, and the purity is high.
The technical scheme of the invention is realized as follows: a preparation method of dioxopromethazine hydrochloride comprises the following steps:
(1) and (3) oxidation reaction: the solution A contains free promethazine, potassium hydrogen persulfate solution is dripped into the solution A under the condition of low temperature, stirring is carried out continuously in the dripping process, and the promethazine is oxidized into dioxopromethazine to obtain solution B;
(2) salt forming reaction: dissociating the dioxopromethazine in the solution B into dichloromethane by using sodium hydroxide, washing an organic phase with water, removing a solvent, dissolving the organic phase after the solvent is removed by using acetone, and introducing hydrogen chloride gas into the acetone to prepare a dioxopromethazine hydrochloride crude product;
(3) and (3) refining reaction: dissociating the crude dioxopromethazine hydrochloride into dioxopromethazine by using sodium hydroxide, dissolving the dissociated dioxopromethazine base in acetone, decolorizing with activated carbon, filtering, and introducing hydrogen chloride gas into acetone to obtain a refined dioxopromethazine hydrochloride.
Further, in the step (1), the solution A is prepared by the following method:
1) adding purified water and cyclohexane into promethazine hydrochloride or promethazine oxalate, stirring, dripping sodium hydroxide solution at 10-30 deg.C, adjusting pH of the mixed solution to 9-12, stirring for 10-30min, standing for layering, separating out organic phase, and washing the organic phase with purified water for multiple times;
2) cooling the organic phase washed in the step 1) to 0-30 ℃, slowly dripping sulfuric acid solution, stirring for 30-60min after dripping is finished, then heating to 20-60 ℃, stirring, standing and layering to obtain a solution A of promethazine bisulfate aqueous solution.
Further, in the step (1), the solution A is cooled to 0-20 ℃, a potassium hydrogen persulfate solution is slowly added, after the addition, the reaction is carried out for 15-45min under the condition of heat preservation, the temperature is heated to 10-40 ℃, the reaction is carried out for 4-5h, and the promethazine is oxidized into dioxopromethazine, so as to obtain a solution B.
Further, in the step (2), dichloromethane is added into the solution B at the temperature of below 20 ℃, the mixture is uniformly stirred, then sodium hydroxide solution is dripped until the PH value is 9-12, the mixture is stirred for 10-30min, the mixture is kept stand and layered, dichloromethane is used for extraction twice, organic phases are combined, water is used for extraction and washing of the organic phases twice, layering is carried out, and decompression and solvent removal are carried out on the organic phases to obtain dioxopromethazine;
heating and dissolving dioxopromethazine with acetone to obtain solution C, and cooling the solution C to room temperature. And introducing hydrogen chloride gas until the pH value reaches 2-4, stopping introducing the gas, stirring for 10-30min, cooling to 0-10 ℃, preserving the temperature for 1-2h, filtering, and leaching with acetone to obtain a dioxopromethazine hydrochloride crude product.
Further, in the step (3), adding purified water and cyclohexane into the dioxopromethazine hydrochloride crude product, stirring uniformly, then dripping sodium hydroxide solution at 10-30 ℃, adjusting the pH of the mixed solution to 9-12, stirring for 10-30min, standing for layering, separating out an organic phase, and washing the organic phase with purified water for multiple times;
heating and dissolving the organic phase by using acetone, cooling to room temperature, decoloring by using activated carbon, performing suction filtration, introducing hydrogen chloride gas into the acetone until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 10-30min, cooling to 0-10 ℃, preserving heat for 1-2h, filtering, leaching by using the acetone to obtain a filter cake, and performing vacuum drying on the filter cake.
Further, in the step 1), 70-90ml of purified water and 70-90ml of cyclohexane are added into 15-30g of promethazine hydrochloride or promethazine oxalate; in the step 2), the sulfuric acid solution is prepared by adopting 4-5g of sulfuric acid and 40ml of purified water.
Further, in the step (1), a potassium hydrogen persulfate solution was prepared using 40 to 50g of potassium hydrogen persulfate and 160mL of purified water.
Dioxypromazine hydrochloride, which is prepared by the preparation method.
The invention has the beneficial effects that:
the method adopts the potassium hydrogen persulfate as the oxidant, has simple and safe operation, low requirement on equipment, certain acid and alkali resistance, and no need of pressurization; the energy consumption is low, unlike a hydrogen peroxide oxidation system, heating or reflux is required; the dioxopromethazine hydrochloride with higher yield can be obtained, and the purity is high and can reach more than 98 percent; furthermore, potassium hydrogen persulfate is used as an oxidizing agent, so that the raw material is cheap, and the generated wastewater is well treated.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without inventive effort based on the embodiments of the present invention, are within the scope of the present invention.
Example one
A preparation method of dioxopromethazine hydrochloride comprises the following steps:
(1) and (3) oxidation reaction: and (3) cooling the solution A to 10 ℃, slowly adding a potassium hydrogen persulfate solution, keeping the temperature for reaction for 25min after the addition is finished, heating to 30 ℃, keeping the temperature for 5h, oxidizing promethazine into dioxopromethazine to obtain a solution B, wherein the potassium hydrogen persulfate solution is prepared from 45.74g of potassium hydrogen persulfate and 160mL of purified water.
Solution a was prepared using the following method:
1) adding 20g of promethazine hydrochloride into a flask, adding 80ml of purified water and 80ml of cyclohexane, uniformly stirring, then dropwise adding a 15 wt% sodium hydroxide aqueous solution at 30 ℃, adjusting the pH value of the mixed solution to 10, stirring for 20min, standing for layering, separating out an organic phase, and washing the organic phase with purified water for 2 times;
2) placing the organic phase (promethazine cyclohexane solution) washed in the step 1) into a flask, cooling to 5 ℃, slowly dropwise adding a sulfuric acid solution, preparing the sulfuric acid solution by adopting 4.21g of sulfuric acid and 40ml of purified water, stirring for 40min after dropwise adding, then heating to 50 ℃, stirring, standing and layering to obtain a solution A promethazine bisulfate aqueous solution.
In the step (1), the reaction formula for oxidizing promethazine into dioxopromethazine is as follows:
(2) salt forming reaction: adding dichloromethane into the solution B at the temperature of below 20 ℃, uniformly stirring, then dropwise adding 10 wt% of sodium hydroxide solution until the pH value is 10, stirring for 25min, standing for layering, extracting twice with dichloromethane, combining organic phases, extracting and washing the organic phase twice with water, layering, and removing the solvent from the organic phase under reduced pressure to obtain dioxopromethazine;
heating and dissolving dioxopromethazine with acetone to obtain a solution C, cooling the solution C to room temperature, introducing hydrogen chloride gas (HCl) until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 25min, cooling to 0 ℃, keeping the temperature for 1.5h, filtering, and leaching with acetone to obtain a dioxopromethazine hydrochloride crude product.
The formula for reacting dioxopromethazine with HCl to form dioxopromethazine hydrochloride is as follows:
(3) and (3) refining reaction: adding 80ml of purified water and 80ml of cyclohexane into the dioxopromethazine hydrochloride crude product, uniformly stirring, then dropwise adding 15 wt% of sodium hydroxide aqueous solution at the temperature of 30 ℃, adjusting the pH value of the mixed solution to 10, stirring for 20min, standing for layering, separating out an organic phase, washing the organic phase for multiple times by using purified water, wherein the organic phase contains free dioxopromethazine base;
heating and dissolving the organic phase by using acetone, cooling to room temperature, decoloring by using activated carbon, performing suction filtration, introducing hydrogen chloride gas into the acetone until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 25min, cooling to 0 ℃, keeping the temperature for 1.5h, filtering, leaching by using the acetone to obtain a filter cake, and performing vacuum drying on the filter cake at 50 ℃ to obtain 19.02g of dioxopromethazine hydrochloride with the purity of 98.04%.
Example two
A preparation method of dioxopromethazine hydrochloride comprises the following steps:
(1) and (3) oxidation reaction: and (3) cooling the solution A to 0 ℃, slowly adding a potassium hydrogen persulfate solution, carrying out heat preservation reaction for 15min after the solution A is added, heating to 10 ℃, carrying out heat preservation for 4h, oxidizing promethazine into dioxopromethazine to obtain a solution B, wherein the potassium hydrogen persulfate solution is prepared from 40g of potassium hydrogen persulfate and 160mL of purified water.
Solution a was prepared using the following method:
1) adding 15g of promethazine hydrochloride into a flask, adding 70ml of purified water and 70ml of cyclohexane, uniformly stirring, then dropwise adding a 15 wt% aqueous solution of sodium hydroxide at 10 ℃, adjusting the pH value of the mixed solution to 9, stirring for 10min, standing for layering, separating out an organic phase, and washing the organic phase with purified water for 2 times;
2) placing the organic phase (promethazine cyclohexane solution) washed in the step 1) into a flask, cooling to 0 ℃, slowly dropwise adding a sulfuric acid solution, preparing the sulfuric acid solution by adopting 4g of sulfuric acid and 40ml of purified water, stirring for 30min after dropwise adding, then heating to 20 ℃, stirring, standing for layering, and obtaining a promethazine bisulfate aqueous solution A.
(2) Salt forming reaction: adding dichloromethane into the solution B at the temperature of below 20 ℃, uniformly stirring, then dropwise adding 10 wt% of sodium hydroxide solution until the pH value is 9, stirring for 10min, standing for layering, extracting twice with dichloromethane, combining organic phases, extracting and washing the organic phase twice with water, layering, and removing the solvent from the organic phase under reduced pressure to obtain dioxopromethazine;
heating and dissolving dioxopromethazine with acetone to obtain a solution C, cooling the solution C to room temperature, introducing hydrogen chloride gas until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 10min, cooling to 5 ℃, keeping the temperature for 1h, filtering, and leaching with acetone to obtain a dioxopromethazine hydrochloride crude product.
(3) And (3) refining reaction: adding 70ml of purified water and 70ml of cyclohexane into the dioxopromethazine hydrochloride crude product, uniformly stirring, then dropwise adding a 15 wt% aqueous solution of sodium hydroxide at 10 ℃, adjusting the pH of the mixed solution to 9, stirring for 10min, standing for layering, separating out an organic phase, washing the organic phase for multiple times by using purified water, wherein the organic phase contains free dioxopromethazine bases;
heating and dissolving the organic phase by using acetone, cooling to room temperature, decoloring by using activated carbon, performing suction filtration, introducing hydrogen chloride gas into the acetone until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 10min, cooling to 5 ℃, preserving the temperature for 1h, filtering, leaching by using acetone to obtain a filter cake, and performing vacuum drying on the filter cake at 50 ℃ to obtain 14.23g of dioxopromethazine hydrochloride with the purity of 98.13%.
EXAMPLE III
A preparation method of dioxopromethazine hydrochloride comprises the following steps:
(1) and (3) oxidation reaction: and (3) cooling the solution A to 5 ℃, slowly adding a potassium hydrogen persulfate solution, keeping the temperature for reaction for 35min after the addition is finished, heating to 20 ℃, keeping the temperature for 4.5h, oxidizing promethazine into dioxopromethazine to obtain a solution B, and preparing the potassium hydrogen persulfate solution by adopting 45g of potassium hydrogen persulfate and 160mL of purified water.
Solution a was prepared using the following method:
1) adding 25g of promethazine hydrochloride into a flask, adding 80ml of purified water and 80ml of cyclohexane, uniformly stirring, then dropwise adding 15 wt% of sodium hydroxide solution at 20 ℃, adjusting the pH value of the mixed solution to 12, stirring for 30min, standing for layering, separating out an organic phase, and washing the organic phase with purified water for 2 times;
2) placing the organic phase (promethazine cyclohexane solution) washed in the step 1) into a flask, cooling to 10 ℃, slowly dropwise adding a sulfuric acid solution, preparing the sulfuric acid solution by adopting 4.8g of sulfuric acid and 40ml of purified water, stirring for 50min after dropwise adding, then heating to 40 ℃, stirring, standing and layering to obtain a solution A promethazine bisulfate aqueous solution.
(2) Salt forming reaction: adding dichloromethane into the solution B at the temperature of below 20 ℃, uniformly stirring, then dropwise adding 10 wt% of sodium hydroxide solution until the pH value is 11, stirring for 20min, standing for layering, extracting twice with dichloromethane, combining organic phases, extracting and washing the organic phase twice with water, layering, and removing the solvent from the organic phase under reduced pressure to obtain dioxopromethazine;
heating and dissolving dioxopromethazine with acetone to obtain a solution C, cooling the solution C to room temperature, introducing hydrogen chloride gas until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 20min, cooling to 10 ℃, keeping the temperature for 1.5h, filtering, and leaching with acetone to obtain a dioxopromethazine hydrochloride crude product.
(3) And (3) refining reaction: adding 80ml of purified water and 80ml of cyclohexane into the dioxopromethazine hydrochloride crude product, uniformly stirring, then dropwise adding a 15 wt% aqueous solution of sodium hydroxide at 20 ℃, adjusting the pH of the mixed solution to 12, stirring for 30min, standing for layering, separating out an organic phase, washing the organic phase for multiple times by using purified water, wherein the organic phase contains free dioxopromethazine bases;
heating and dissolving the organic phase by using acetone, cooling to room temperature, decoloring by using activated carbon, performing suction filtration, introducing hydrogen chloride gas into the acetone until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 20min, cooling to 10 ℃, preserving the temperature for 1.5h, filtering, leaching by using the acetone to obtain a filter cake, and performing vacuum drying on the filter cake at 50 ℃ to obtain 23.73g of dioxopromethazine hydrochloride with the purity of 98.21%.
Example four
A preparation method of dioxopromethazine hydrochloride comprises the following steps:
(1) and (3) oxidation reaction: and (3) cooling the solution A to 20 ℃, slowly adding a potassium hydrogen persulfate solution, keeping the temperature for reaction for 45min after the addition is finished, heating to 40 ℃, keeping the temperature for 5h, oxidizing promethazine into dioxopromethazine to obtain a solution B, wherein the potassium hydrogen persulfate solution is prepared from 50g of potassium hydrogen persulfate and 160mL of purified water.
Solution a was prepared using the following method:
1) adding 30g of promethazine hydrochloride into a flask, adding 90ml of purified water and 90ml of cyclohexane, uniformly stirring, then dropwise adding 15 wt% of sodium hydroxide solution at 30 ℃, adjusting the pH value of the mixed solution to 12, stirring for 30min, standing for layering, separating out an organic phase, and washing the organic phase with purified water for 2 times;
2) placing the organic phase (promethazine cyclohexane solution) washed in the step 1) into a flask, keeping the temperature at 30 ℃, slowly dropwise adding a sulfuric acid solution, preparing the sulfuric acid solution by adopting 5g of sulfuric acid and 40ml of purified water, stirring for 60min after dropwise adding, then heating to 60 ℃, stirring, standing for layering, and obtaining a promethazine bisulfate aqueous solution A.
(2) Salt forming reaction: adding dichloromethane into the solution B at the temperature of below 20 ℃, uniformly stirring, then dropwise adding 10 wt% of sodium hydroxide solution until the pH value is 12, stirring for 30min, standing for layering, extracting twice with dichloromethane, combining organic phases, extracting and washing the organic phase twice with water, layering, and removing the solvent from the organic phase under reduced pressure to obtain dioxopromethazine;
heating and dissolving dioxopromethazine with acetone to obtain a solution C, cooling the solution C to room temperature, introducing hydrogen chloride gas until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 30min, cooling to 5 ℃, keeping the temperature for 2h, filtering, and leaching with acetone to obtain a dioxopromethazine hydrochloride crude product.
(3) And (3) refining reaction: adding 90ml of purified water and 90ml of cyclohexane into the dioxopromethazine hydrochloride crude product, uniformly stirring, then dropwise adding a 15 wt% aqueous solution of sodium hydroxide at the temperature of 30 ℃, adjusting the pH of the mixed solution to 12, stirring for 30min, standing for layering, separating out an organic phase, washing the organic phase for multiple times by using purified water, wherein the organic phase contains free dioxopromethazine bases;
heating and dissolving the organic phase by using acetone, cooling to room temperature, decoloring by using activated carbon, performing suction filtration, introducing hydrogen chloride gas into the acetone until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 30min, cooling to 5 ℃, preserving the temperature for 2h, filtering, leaching by using acetone to obtain a filter cake, and performing vacuum drying on the filter cake at 50 ℃ to obtain 28.52g of dioxopromethazine hydrochloride with the purity of 98.09%.
EXAMPLE five
This example is essentially the same as example one except that in step 1), promethazine hydrochloride was replaced with promethazine oxalate.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (8)
1. The preparation method of dioxopromethazine hydrochloride is characterized by comprising the following steps:
(1) and (3) oxidation reaction: the solution A contains free promethazine, potassium hydrogen persulfate solution is dripped into the solution A under the condition of low temperature, stirring is carried out continuously in the dripping process, and the promethazine is oxidized into dioxopromethazine to obtain solution B;
(2) salt forming reaction: dissociating the dioxopromethazine in the solution B into dichloromethane by using sodium hydroxide, washing an organic phase with water, removing a solvent, dissolving the organic phase after the solvent is removed by using acetone, and introducing hydrogen chloride gas into the acetone to prepare a dioxopromethazine hydrochloride crude product;
(3) and (3) refining reaction: dissociating the crude dioxopromethazine hydrochloride into dioxopromethazine base by using sodium hydroxide, dissolving the dissociated dioxopromethazine base in acetone, decolorizing with activated carbon, vacuum-filtering, and introducing hydrogen chloride gas into acetone to obtain a refined dioxopromethazine hydrochloride.
2. The method for preparing dioxopromazine hydrochloride according to claim 1, wherein in the step (1), the solution A is prepared by the following method:
1) adding purified water and cyclohexane into promethazine hydrochloride or promethazine oxalate, stirring, dripping sodium hydroxide solution at 10-30 deg.C, adjusting pH of the mixed solution to 9-12, stirring for 10-30min, standing for layering, separating out organic phase, and washing the organic phase with purified water for multiple times;
2) cooling the organic phase washed in the step 1) to 0-30 ℃, slowly dripping sulfuric acid solution, stirring for 30-60min after dripping is finished, then heating to 20-60 ℃, stirring, standing and layering to obtain a solution A of promethazine bisulfate aqueous solution.
3. The method for preparing dioxypromazine hydrochloride according to claim 1, wherein in step (1), the solution A is cooled to 0-20 ℃, the potassium hydrogen persulfate solution is slowly added, after the addition, the reaction is carried out for 15-45min under the condition of heat preservation, the solution is heated to 10-40 ℃, the reaction is carried out for 4-5h under the condition of heat preservation, and the promethazine is oxidized into dioxypromethazine to obtain the solution B.
4. The method for preparing dioxopromethazine hydrochloride according to claim 1, wherein in the step (2), dichloromethane is added into the solution B at a temperature below 20 ℃, the mixture is uniformly stirred, then sodium hydroxide solution is added dropwise until the pH value is 9-12, the mixture is stirred for 10-30min, the mixture is kept stand for layering, dichloromethane is used for extracting twice, organic phases are combined, water is used for extracting and washing the organic phase twice, layering is carried out, and the organic phase is subjected to reduced pressure desolventization to obtain dioxopromethazine base;
heating and dissolving dioxopromethazine base with acetone to obtain solution C, cooling the solution C to room temperature, introducing hydrogen chloride gas until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 10-30min, cooling to 0-10 ℃, preserving heat for 1-2h, filtering, and leaching with acetone to obtain a dioxopromethazine hydrochloride crude product.
5. The method for preparing dioxopromethazine hydrochloride according to claim 1, wherein in step (3), purified water and cyclohexane are added to the dioxopromethazine hydrochloride crude product, the mixture is stirred uniformly, then sodium hydroxide solution is dropped at 10-30 ℃, the pH of the mixed solution is adjusted to 9-12, the mixture is stirred for 10-30min, the mixture is kept stand for layering, an organic phase is separated, and the organic phase is washed with purified water for multiple times;
heating and dissolving the organic phase by using acetone, cooling to room temperature, decoloring by using activated carbon, performing suction filtration, introducing hydrogen chloride gas into the acetone until the pH value reaches 2-4, stopping introducing the hydrogen chloride gas, stirring for 10-30min, cooling to 0-10 ℃, preserving heat for 1-2h, filtering, leaching by using the acetone to obtain a filter cake, and performing vacuum drying on the filter cake.
6. The method for preparing dioxypromazine hydrochloride according to claim 2, wherein in step 1), 70-90ml of purified water and 70-90ml of cyclohexane are added to 15-30g of promethazine hydrochloride or promethazine oxalate; in the step 2), the sulfuric acid solution is prepared by adopting 4-5g of sulfuric acid and 40ml of purified water.
7. The method for preparing dioxopromazine hydrochloride according to claim 1, wherein in the step (1), the potassium hydrogen persulfate solution is prepared from 40-50g of potassium hydrogen persulfate and 160mL of purified water.
8. Dioxopromethazine hydrochloride, obtainable by the process according to any one of claims 1 to 6.
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| CN115703749A (en) * | 2021-08-05 | 2023-02-17 | 河南优凯制药有限公司 | Dioxopropizine hydrochloride nitrogen oxide and preparation method thereof |
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| CN106749098A (en) * | 2016-12-07 | 2017-05-31 | 大连万福制药有限公司 | A kind of friendly process for preparing dioxopromethazine hydrochloride as oxidant with oxygen |
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| CN106749098A (en) * | 2016-12-07 | 2017-05-31 | 大连万福制药有限公司 | A kind of friendly process for preparing dioxopromethazine hydrochloride as oxidant with oxygen |
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| CN115703749A (en) * | 2021-08-05 | 2023-02-17 | 河南优凯制药有限公司 | Dioxopropizine hydrochloride nitrogen oxide and preparation method thereof |
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