CN110683992A - Method for synthesizing econazole nitrate by one-pot method - Google Patents
Method for synthesizing econazole nitrate by one-pot method Download PDFInfo
- Publication number
- CN110683992A CN110683992A CN201911060532.3A CN201911060532A CN110683992A CN 110683992 A CN110683992 A CN 110683992A CN 201911060532 A CN201911060532 A CN 201911060532A CN 110683992 A CN110683992 A CN 110683992A
- Authority
- CN
- China
- Prior art keywords
- koh
- mass ratio
- imidazole
- econazole nitrate
- ethanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/60—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a method for synthesizing econazole nitrate by a one-pot method, which belongs to the technical field of econazole nitrate synthesis methods and comprises the following steps: using 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and imidazole as raw materials, in K2CO3/KOH/A12O3Under the action of PEG-200, obtaining imidazole ethanol containing toluene through N-alkylation reaction; imidazole ethanol containing toluene and p-chlorobenzyl chloride in K2CO3/KOH/A12O3Carrying out O-alkylation reaction with PEG-200 to obtain econazole nitrate; according to the method, the intermediate imidazole ethanol is not required to be washed to be nearly neutral, recrystallized and dried, and is directly subjected to O-alkylation reaction, so that the pollution to the environment caused by drying is reduced, the imidazole ethanol dissolving process is shortened, the reaction efficiency is improved, and the solvent recovery times are reduced; after the O-alkylation reaction is finished, the impurity is removed before acidification, so that the product viscosity caused by more impurities is greatly reduced, the solid-liquid separation is easy to realize, the one-pot discharge is realized, the cost is low, the operation is simple and convenient, and the method is suitable for industrial popularization。
Description
Technical Field
The invention belongs to the technical field of econazole nitrate synthesis methods, and particularly relates to a method for synthesizing econazole nitrate by a one-pot method.
Background
Econazole nitrate is named Econazole nitrate in English and 1- [ 2, 4-dichloro-beta (4-chlorobenzyloxy) phenethyl ] imidazole nitrate in chemical name, is a broad-spectrum antifungal drug, has sterilization and bacteriostasis effects on dermatophytes, saccharomycetes and the like, and is a first-choice drug for clinically treating superficial fungal infection diseases such as tinea cruris, tinea manus and pedis, tinea versicolor, candida dermatitis and the like.
The literature reports that econazole nitrate is synthesized by various methods, 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and imidazole are used as raw materials, NaOH is used as alkali, BuN + Br-is used as a phase transfer catalyst, DMF is used as a solvent, the raw materials react for 5 hours at 80 ℃ to obtain imidazole ethanol crude products, the imidazole ethanol crude products are recrystallized to obtain imidazole ethanol, the imidazole ethanol crude products react with p-chlorobenzyl chloride in NaOH solution which takes TEBA as a catalyst and toluene as a solvent at 80 ℃, nitric acid acidification and 95% ethanol recrystallization are carried out to obtain econazole nitrate, the DMF has a high boiling point, and is unstable (especially at a high temperature) in the presence of strong base such as sodium hydroxide or strong acid and is hydrolyzed into formic acid and dimethylamine, the intermediate imidazole ethanol needs to be recrystallized, is acidified in toluene, has high viscosity, and solid-liquid separation is not easy to realize.
The preparation method comprises the steps of taking 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and imidazole as raw materials, taking NaOH as alkali, taking PEG-400 as a phase transfer catalyst, taking THF as a solvent, carrying out reflux reaction for 3 hours, supplementing NaOH, then carrying out reflux reaction with p-chlorobenzyl chloride in NaOH solution for 4 hours, carrying out nitric acid acidification, distillation and 95% ethanol recrystallization to obtain econazole nitrate, wherein the total yield is 68%.
1- (2, 4-dichlorophenyl) -2-chloro-ethanol and imidazole are used as raw materials, NaOH is used as alkali, 84 type catalyst is used as a phase transfer catalyst, DMF is used as a solvent, the raw materials react for 3 hours at 80 ℃, NaOH is supplemented, the raw materials and p-chlorobenzyl chloride are stirred for 3 hours at 40-50 ℃, nitric acid acidification and ethanol recrystallization are carried out to obtain econazole nitrate, the total yield is 65%, the imidazole ethanol serving as an intermediate of the process is not treated at all, direct O-alkylation is carried out, side reactions are more, impurities are more, ether extraction is needed, the operation is complex, and the yield is low.
Shaohulcheng, etc. takes 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and imidazole as raw materials, NaOH as alkali, TEBA as a phase transfer catalyst and DMF as a solvent, reacts for 5h at 65 ℃ to obtain imidazole ethanol, then reacts with p-chlorobenzyl in 50 percent NaOH solution which takes TEBA as a catalyst and toluene as a solvent for 2h at 100 ℃, and is acidified by nitric acid to obtain econazole nitrate, wherein the total yield is 53.28 percent, and the process has high reaction temperature and low yield.
The preparation method comprises the steps of taking sodium methoxide obtained by reaction of methanol and metal sodium as an alkali and DMF as a solvent, dropwise adding a benzene solution of 1- (2, 4-dichlorophenyl) -2-chloro-ethanol to obtain imidazole ethanol, taking the sodium methoxide as the alkali and the DMF as the solvent, keeping the temperature of the imidazole ethanol and p-chlorobenzyl at 40-50 ℃ for 2 hours, acidifying an ether extracting solution, and recrystallizing the ethanol, wherein the total yield is 23.52%, a plurality of solvents are used for reaction, the reaction temperature is high, and the yield is very low. Benzene is a carcinogen, has a melting point of 5 ℃, and is not easy to operate in winter. The sodium metal is not easy to store, and the sodium methoxide is inflammable, explosive, easy to absorb moisture, and has strong irritation and corrosivity.
From the above, the existing method for synthesizing econazole nitrate has the defects of complicated operation process, low yield, easy harm to people and environment and the like, and the method for synthesizing econazole nitrate, which is simple to operate, green and environment-friendly, and has high yield, still needs to be continuously researched.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a method for synthesizing econazole nitrate by a one-pot method.
The invention aims to provide a method for synthesizing econazole nitrate by a one-pot method, which comprises the following steps:
using 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and imidazole as raw materials, K2CO3/KOH/A12O3I is a multi-component inorganic carrier reagent, PEG-200I is a phase transfer catalyst, and an intermediate mixture is obtained through N-alkylation reaction; adding p-chlorobenzyl chloride to the intermediate mixture, and adding the mixture at K2CO3/KOH/A12O3II, PEG-200 II and K2CO3/KOH/A12O3III, removing impurities, acidifying and recrystallizing to obtain the econazole nitrate through an O-alkylation reaction.
Preferably, in the method for synthesizing econazole nitrate by the one-pot method, the intermediate mixture is prepared by the following steps:
will K2CO3/KOH/A12O3Mixing I, imidazole, toluene I and PEG-200I, heating, refluxing, separating water for 25-35 min, cooling to 60 ℃, adding a mixed solution of 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and toluene II, heating to 71-73 ℃, reacting for 3-3.5 h, filtering, washing, combining filtrate and washing liquor, standing to separate an organic layer, and removing impurities from the organic layer to obtain an intermediate mixture;
said K2CO3/KOH/A12O3I: the mass ratio of imidazole is 2.6-3.4: 1, K2CO3/KOH/A12O3I: the mass ratio of toluene I is 1: 1.8-2.4, and imidazole: the mass ratio of PEG-200I is 8.9-18.8: 1, K2CO3/KOH/A12O3I: the mass ratio of the 1- (2, 4-dichlorophenyl) -2-chloro-ethanol to the 1- (2, 4-dichlorophenyl) -2-chloro-ethanol is 0.8-1.1: 1: the mass ratio of the toluene II is 0.6-0.75: 1.
Preferably, the econazole nitrate is prepared through the following steps:
adding K to the total of said intermediate mixtures obtained2CO3/KOH/A12O3II, isopropanol, PEG-200 II, heating and refluxingWater is cooled to 67 ℃ for 25-35 min, the temperature is reduced to 67 ℃, the mixed solution of p-chlorobenzyl chloride and toluene III is added, the reaction is carried out for 1h at 66-68 ℃, and K is added2CO3/KOH/A12O3III, reacting for 2-2.5 h at 66-68 ℃, filtering, washing, combining the filtrate and the washing liquor, standing to separate an organic layer, removing impurities from the organic layer, acidifying with concentrated nitric acid, and recrystallizing to obtain econazole nitrate;
the imidazole: k2CO3/KOH/A12O3The mass ratio of II is 1: 3.3-4.4, K2CO3/KOH/A12O3II: isopropyl alcohol: the mass ratio of PEG-200 II is 3.3-6.3: 1: 0.02 to 0.06, isopropyl alcohol: the mass ratio of p-chlorobenzyl chloride to p-chlorobenzyl chloride is 1: 1.8-3, and the mass ratio of p-chlorobenzyl chloride to p-chlorobenzyl chloride is as follows: the mass ratio of toluene III is 2.1-3.9: 1, and the mass ratio of toluene III: k2CO3/KOH/A12O3The mass ratio of III is 1: 1.4-4.
Preferably, the recrystallization solvent is absolute ethanol.
Preferably, said K2CO3/KOH/A12O3Ⅰ、K2CO3/KOH/A12O3II and K2CO3/KOH/A12O3The III is prepared by the following steps:
will K2CO3KOH in water, A1 was added2O3Stirring and preserving heat for 1h at the temperature of 60-65 ℃, evaporating the solvent, and drying to obtain the product; said K2CO3: KOH: water: a12O3The mass ratio is 18:7:22: 29.
Compared with the prior art, the invention has the following beneficial effects:
the invention adopts K2CO3/KOH/A12O3The PEG-200 is a multi-component inorganic carrier reagent, and the PEG-200 is a phase transfer catalyst, so that the impurities of a reaction system are reduced, the prepared intermediate mixture (imidazole ethanol containing methylbenzene) is directly subjected to an O-alkylation reaction without recrystallization and drying, the pollution to the environment caused by drying is reduced, the imidazole ethanol dissolving process is shortened, the reaction efficiency is improved, and the water, electricity, manpower and the like caused by recrystallization, drying and dissolving are reducedConsumption, and the recovery times of the solvent are reduced; in addition, impurity removal treatment is firstly carried out before acidification after the O-alkylation reaction is finished, so that the problem of high product viscosity caused by more impurities is greatly reduced, solid-liquid separation is easy to realize, one-pot discharge is realized, the cost is low, the operation is simple and convenient, and the method is suitable for industrial popularization.
Drawings
Fig. 1 is a process flow diagram of a method for synthesizing econazole nitrate by a one-pot method provided by the invention.
Detailed Description
In order to make the technical solutions of the present invention better understood and implemented by those skilled in the art, the present invention is further described below with reference to the following specific embodiments and the accompanying drawings, but the embodiments are not meant to limit the present invention.
Example 1
A method for synthesizing econazole nitrate by a one-pot method is shown in figure 1, and comprises the following steps:
(1)K2CO3/KOH/A12O3the preparation of (1): will 90g K2CO335g KOH in 110g water, 145gA1 was added2O3Stirring at 60 deg.C, maintaining the temperature for 1h, rotary evaporating, drying at 120 deg.C for 4h to obtain 258.7g K2CO3/KOH/A12O3；
(2) Preparing econazole nitrate: 80gK is added2CO3/KOH/A12O3Adding I, 30g of imidazole, 190g of toluene I and 2.5g of PEG-200I into a 500mL reaction bottle, heating up, refluxing and dividing water for 30 minutes, cooling to 60 ℃, dropwise adding a mixed solution of 90g of 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and 120g of toluene II, heating to 72 ℃, and reacting for 3.5 hours; filtering, washing with water, combining the filtrate and the washing liquor, standing to separate an organic layer, washing the organic layer with water once, adding 0.5g of activated carbon I, preserving heat for 10 minutes, and carrying out hot filtration to obtain imidazole ethanol containing toluene;
to the total amount of the obtained imidazole ethanol containing toluene was added 100g K2CO3/KOH/A12O3II, 25g of isopropanol and 1g of PEG-200 II, heating, refluxing, dividing water for 30 minutes, cooling to 67 ℃, adding 53g of p-chlorobenzyl chloride and 20g of methylThe mixed solution of benzene III reacts for 1h at 67 ℃, and 60g K is added2CO3/KOH/A12O3III, reacting at 67 ℃ for 2.5h, filtering, washing with water, combining filtrate and washing liquor, standing to separate an organic layer, adding water, washing to be neutral, standing for layering, adding 0.8g of activated carbon II into an upper material layer, preserving heat for 10 minutes, performing heat filtration, slightly cooling, dropwise adding 34g of concentrated nitric acid for acidification, filtering, leaching a filter cake with water, dissolving the filter cake with 400g of absolute ethyl alcohol, refluxing for 10 minutes, cooling to room temperature, then cooling to 4 ℃ in an ice water mixture, separating out white crystals, filtering, and drying the obtained filter cake to constant weight at 60 ℃ to obtain 134.2g of econazole nitrate, wherein the total yield is 75.6%. Measured by a capillary melting point method, m.p.164.6-165.3 ℃.
Example 2
A method for synthesizing econazole nitrate by a one-pot method comprises the following steps:
(1)K2CO3/KOH/A12O3the preparation of (1): will 90g K2CO335g KOH in 110g water, 145gA1 was added2O3Stirring at 65 deg.C, maintaining for 1 hr, rotary evaporating, and drying at 120 deg.C for 4 hr to obtain 257.6g K2CO3/KOH/A12O3；
(2) Preparing econazole nitrate: mixing 90gK2CO3/KOH/A12O3Adding 29.5g of imidazole, 180g of toluene I and 1.6g of PEG-200I into a 500mL reaction bottle, heating, refluxing and dividing water for 25 minutes, cooling to 60 ℃, dropwise adding a mixed solution of 90g of 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and 130g of toluene II, heating to 71 ℃, and reacting for 3.0 hours. Filtering, washing with water, combining the filtrate and the washing liquor, standing to separate an organic layer, washing the organic layer with water once, adding 0.7g of activated carbon I, preserving heat for 10 minutes, and carrying out hot filtration to obtain imidazole ethanol containing toluene;
to the total amount of the above-obtained imidazole ethanol containing toluene was added 115g K2CO3/KOH/A12O3II, 30g of isopropanol and 1.2g of PEG-200 II, heating, refluxing, dividing water for 25 minutes, cooling to 67 ℃, adding a mixed solution of 56g of p-chlorobenzyl chloride and 15g of toluene III, reacting for 1 hour at 66 ℃, and adding 45g K2CO3/KOH/A12O3III, reacting at 66 ℃ for 2.0h, filtering, washing with water, combining filtrate and washing liquor, standing to separate an organic layer, adding water, washing to be neutral, standing for layering, adding 1g of activated carbon II into an upper material layer, preserving heat for 10 minutes, performing heat filtration, slightly cooling, dropwise adding 38g of concentrated nitric acid for acidification, filtering, leaching a filter cake with water, dissolving the filter cake with 380g of absolute ethyl alcohol, refluxing for 10 minutes, cooling to room temperature, then cooling to 2 ℃ in an ice water mixture, separating out white crystals, filtering, and drying the obtained filter cake to constant weight at 60 ℃ to obtain 132.6g of econazole nitrate, wherein the total yield is 74.7%. Measured by a capillary melting point method, m.p.164.2-165.1 ℃.
Example 3
A method for synthesizing econazole nitrate by a one-pot method comprises the following steps:
(1)K2CO3/KOH/A12O3the preparation of (1): will 90g K2CO335g KOH in 110g water, 145gA1 was added2O3Stirring at 62 deg.C, maintaining for 1h, rotary evaporating, drying at 120 deg.C for 4h to obtain 256.5g K2CO3/KOH/A12O3；
(2) Preparing econazole nitrate: mixing 95gK2CO3/KOH/A12O3Adding 28.6g of imidazole, 170g of toluene I and 3.2g of PEG-200I into a 500mL reaction bottle, heating up, refluxing and dividing water for 35min, cooling to 60 ℃, dropwise adding a mixed solution of 90g of 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and 140g of toluene II, heating to 73 ℃, and reacting for 3.5 h; filtering, washing with water, mixing the filtrate and washing liquid, standing to separate out an organic layer, washing the organic layer with water once, adding 0.9g of activated carbon I, keeping the temperature for 10min, and performing hot filtration to obtain imidazole ethanol containing toluene;
125g K was added to the total toluene-containing imidazole ethanol obtained2CO3/KOH/A12O3II, 20g of isopropanol and 0.8g of PEG-200 II, heating, refluxing, dividing water for 35 minutes, cooling to 67 ℃, adding a mixed solution of 59g of p-chlorobenzyl chloride and 25g of toluene III, reacting for 1 hour at 68 ℃, and supplementing 35g K2CO3/KOH/A12O3III, reacting at 68 ℃ for 2.5h, filtering, washing with water, and combining the filtrate and the washing liquidStanding to separate an organic layer, adding water, washing to be nearly neutral, standing to layer, adding 1.2g of activated carbon II into an upper material layer, keeping the temperature for 10 minutes, carrying out heat filtration, slightly cooling, dropwise adding 30g of concentrated nitric acid for acidification, filtering, leaching a filter cake with water, dissolving the filter cake with 390g of absolute ethyl alcohol, refluxing for 10 minutes, cooling to room temperature, then cooling to 0 ℃ in an ice-water mixture, separating out white crystals, filtering, drying the obtained filter cake to constant weight at 60 ℃, obtaining 131.9g of econazole nitrate, and obtaining the total yield of 74.3%. Measured by a capillary melting point method, m.p.164.3-165.3 ℃.
According to the embodiment, the econazole nitrate is successfully prepared by the method, the intermediate imidazole ethanol does not need to be recrystallized and dried, the environmental pollution caused by drying is reduced, the imidazole ethanol dissolving process is shortened, the reaction efficiency is improved, the consumption of water, electricity, manpower and the like caused by recrystallization, drying and dissolving is reduced, the solvent recovery frequency is reduced, the purification and impurity removal are carried out before acidification after the O-alkylation reaction is finished, the product viscosity caused by more impurities is greatly reduced, the solid-liquid separation is easy to realize, one-pot extraction is realized, the cost is low, the operation is simple and convenient, and the method is suitable for industrial popularization.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, it is intended that such changes and modifications be included within the scope of the appended claims and their equivalents.
Claims (5)
1. A method for synthesizing econazole nitrate by a one-pot method is characterized by comprising the following steps:
using 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and imidazole as raw materials, K2CO3/KOH/A12O3I is a multi-component inorganic carrier reagent, PEG-200I is a phase transfer catalyst, and an intermediate mixture is obtained through N-alkylation reaction; adding p-chlorobenzyl chloride to the intermediate mixture, and adding the mixture at K2CO3/KOH/A12O3II, PEG-200 II and K2CO3/KOH/A12O3III, removing impurities, acidifying and recrystallizing to obtain the econazole nitrate through an O-alkylation reaction.
2. The one-pot synthesis method of econazole nitrate according to claim 1, wherein the intermediate mixture is specifically prepared by the following steps:
will K2CO3/KOH/A12O3Mixing I, imidazole, toluene I and PEG-200I, heating, refluxing and carrying out water diversion for 25-35 min, cooling to 60 ℃, adding a mixed solution of 1- (2, 4-dichlorophenyl) -2-chloro-ethanol and toluene II, heating to 71-73 ℃, reacting for 3-3.5 h, filtering, washing, combining filtrate and washing liquor, standing to separate an organic layer, and removing impurities from the organic layer to obtain an intermediate mixture;
said K2CO3/KOH/A12O3I: the mass ratio of imidazole is 2.6-3.4: 1, K2CO3/KOH/A12O3I: the mass ratio of toluene I is 1: 1.8-2.4, and imidazole: the mass ratio of PEG-200I is 8.9-18.8: 1, K2CO3/KOH/A12O3I: the mass ratio of the 1- (2, 4-dichlorophenyl) -2-chloro-ethanol to the 1- (2, 4-dichlorophenyl) -2-chloro-ethanol is 0.8-1.1: 1: the mass ratio of the toluene II is 0.6-0.75: 1.
3. The method for synthesizing econazole nitrate by the one-pot method as claimed in claim 1, wherein the econazole nitrate is prepared by the following steps:
adding K to the total of said intermediate mixtures obtained2CO3/KOH/A12O3II, isopropanol and PEG-200 II, heating, refluxing, separating water for 25-35 min, cooling to 67 ℃, adding a mixed solution of p-chlorobenzyl chloride and toluene III, reacting for 1h at 66-68 ℃, and supplementing K2CO3/KOH/A12O3III, reacting for 2-2.5 h at 66-68 ℃, filtering, washing, combining the filtrate and the washing liquor, standing to separate an organic layer, removing impurities from the organic layer, acidifying with concentrated nitric acid, and recrystallizing to obtain econazole nitrate;
the imidazole: k2CO3/KOH/A12O3The mass ratio of II is 1: 3.3-4.4, K2CO3/KOH/A12O3II: isopropyl alcohol: the mass ratio of PEG-200 II is 3.3-6.3: 1: 0.02 to 0.06, isopropyl alcohol: the mass ratio of p-chlorobenzyl chloride to p-chlorobenzyl chloride is 1: 1.8-3, and the mass ratio of p-chlorobenzyl chloride to p-chlorobenzyl chloride is as follows: the mass ratio of toluene III is 2.1-3.9: 1, and the mass ratio of toluene III: k2CO3/KOH/A12O3The mass ratio of III is 1: 1.4-4.
4. The one-pot synthesis method of econazole nitrate according to claim 3, wherein the recrystallization solvent is absolute ethanol.
5. The one-pot synthesis method of econazole nitrate according to claim 1, wherein K is2CO3/KOH/A12O3Ⅰ、K2CO3/KOH/A12O3II and K2CO3/KOH/A12O3The III is prepared by the following steps:
will K2CO3KOH in water, A1 was added2O3Stirring and preserving heat for 1h at the temperature of 60-65 ℃, evaporating the solvent, and drying to obtain the product; said K2CO3: KOH: water: a12O3The mass ratio is 18:7:22: 29.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911060532.3A CN110683992B (en) | 2019-11-01 | 2019-11-01 | Method for synthesizing econazole nitrate by one-pot method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911060532.3A CN110683992B (en) | 2019-11-01 | 2019-11-01 | Method for synthesizing econazole nitrate by one-pot method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110683992A true CN110683992A (en) | 2020-01-14 |
| CN110683992B CN110683992B (en) | 2021-02-26 |
Family
ID=69115324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911060532.3A Active CN110683992B (en) | 2019-11-01 | 2019-11-01 | Method for synthesizing econazole nitrate by one-pot method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110683992B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111187216A (en) * | 2020-03-23 | 2020-05-22 | 徐州工业职业技术学院 | Method for synthesizing imidazole ethanol by continuous method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102399192A (en) * | 2011-12-20 | 2012-04-04 | 扬子江药业集团南京海陵药业有限公司 | Method for preparing isoconazole nitrate |
| CN104860887A (en) * | 2015-05-22 | 2015-08-26 | 池州中瑞化工有限公司 | Synthesis method of 1-(2,4-dichlorophenyl)-2-(1-imidazolyl)-ethanol |
| WO2017216722A2 (en) * | 2016-06-13 | 2017-12-21 | Vyome Biosciences Pvt. Ltd. | Synergistic antifungal compositions and methods thereof |
| CN108503589A (en) * | 2018-06-20 | 2018-09-07 | 徐州工业职业技术学院 | A kind of preparation method of econazole nitrate |
| CN109111402A (en) * | 2018-10-30 | 2019-01-01 | 徐州工业职业技术学院 | A kind of preparation method of imidazolyl ethanol |
-
2019
- 2019-11-01 CN CN201911060532.3A patent/CN110683992B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102399192A (en) * | 2011-12-20 | 2012-04-04 | 扬子江药业集团南京海陵药业有限公司 | Method for preparing isoconazole nitrate |
| CN104860887A (en) * | 2015-05-22 | 2015-08-26 | 池州中瑞化工有限公司 | Synthesis method of 1-(2,4-dichlorophenyl)-2-(1-imidazolyl)-ethanol |
| WO2017216722A2 (en) * | 2016-06-13 | 2017-12-21 | Vyome Biosciences Pvt. Ltd. | Synergistic antifungal compositions and methods thereof |
| CN108503589A (en) * | 2018-06-20 | 2018-09-07 | 徐州工业职业技术学院 | A kind of preparation method of econazole nitrate |
| CN109111402A (en) * | 2018-10-30 | 2019-01-01 | 徐州工业职业技术学院 | A kind of preparation method of imidazolyl ethanol |
Non-Patent Citations (4)
| Title |
|---|
| SEBASTIAN COGSWELL,ET AL.: "A Parenteral Econazole Formulation Using a Novel Micelle-to-Liposome Transfer Method: In Vitro Characterization and Tumor Growth Delay in a Breast Cancer Xenograft Model", 《PHARMACEUTICAL RESEARCH》 * |
| 李再峰等: "咪唑和三唑醚类化合物的合成及生物活性", 《精细化工》 * |
| 王明慧等: "咪康唑和益康唑的PEG-400连续催化N-和O-烷基化反应制备", 《中国医药工业杂志》 * |
| 邵律成等: "正交设计法优化硝酸益康唑的合成工艺", 《药物化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111187216A (en) * | 2020-03-23 | 2020-05-22 | 徐州工业职业技术学院 | Method for synthesizing imidazole ethanol by continuous method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110683992B (en) | 2021-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111377826A (en) | Green synthesis process of key intermediate of quinolone | |
| CN110683992B (en) | Method for synthesizing econazole nitrate by one-pot method | |
| CN101693649B (en) | Process for preparing 1.3.5-trimethoxybenzene | |
| CN112300071B (en) | Synthetic method of high-purity chloroquine phosphate | |
| CN108558679A (en) | A kind of synthetic method of Parylene A presomas | |
| CN115466249A (en) | Preparation method of flumioxazin | |
| CN111747926B (en) | Improved synthetic process method of topiramate free base | |
| CN111253272B (en) | Method for preparing benzamide compound | |
| CN110878043B (en) | Synthetic method of intermediate 6-methoxypyridine-3-formaldehyde of antihypertensive drugs of dipine class | |
| NL2024500B1 (en) | Method for preparing 4-(3-hydroxyphenyl)-4-oxobutanoic acid from lignin | |
| WO2021127965A1 (en) | Method for recycling voriconazole enantiomer | |
| CN113214041A (en) | Novel method for preparing 3-iodine-2 bromotoluene | |
| CN112430197A (en) | Synthesis method of tert-butyl 3-oxo-5-hydroxy-6-cyanohexanoate | |
| CN111533691A (en) | Preparation method of Rosxastat | |
| CN115536494B (en) | Synthesis method of 1- (4-bromophenyl) -1, 4-butanediol | |
| CN111777524B (en) | Post-treatment method for preparing naphthol AS-PH | |
| CN114957042B (en) | Synthesis process of 2, 2-trifluoroacetamidine | |
| CN110156696B (en) | Preparation method of 1, 4-dichlorophthalazine | |
| CN115466255B (en) | Tropine and synthetic method thereof | |
| CN110642770B (en) | Preparation method of 5-methoxyindole | |
| CN112794837B (en) | Synthesis method of heterochroman compound | |
| CN112694450B (en) | Preparation method of 4-methyl-5-ethoxy oxazole | |
| CN113354623B (en) | Preparation method of ilaprazole key intermediate 5- (1H-pyrrole-1-yl) -2-mercaptobenzimidazole | |
| CN115286568B (en) | Preparation method of 2-hydroxy-4-trifluoromethyl pyridine | |
| CN112624901B (en) | Method for refining chiral alcohol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |