CN111454215A - Process for synthesizing 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde by continuous flow ozone oxidation - Google Patents
Process for synthesizing 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde by continuous flow ozone oxidation Download PDFInfo
- Publication number
- CN111454215A CN111454215A CN202010352384.9A CN202010352384A CN111454215A CN 111454215 A CN111454215 A CN 111454215A CN 202010352384 A CN202010352384 A CN 202010352384A CN 111454215 A CN111454215 A CN 111454215A
- Authority
- CN
- China
- Prior art keywords
- ozone
- liquid
- gas
- acetaldehyde
- continuous flow
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a process for synthesizing 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde by continuous flow ozone oxidation, which comprises the following steps: 5-allyl-4, 6-dichloropyrimidine is used as a raw material, and is subjected to continuous flow ozonization and reduction by sodium thiosulfate to obtain a target product. The invention provides a novel continuous flow process for ozonizing and synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde, which is safe, simple to operate, high-efficiency and easy for large-scale production.
Description
Technical Field
The invention relates to a synthesis process, in particular to a process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation.
Background
The CAS number of 4, 6-dichloropyrimidine-5-acetaldehyde is 16019-33-3, the name of the Chinese is 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde, and the molecular formula is C6H4Cl2N20The compound is an important chemical intermediate, and the specific chemical structural formula is as follows:
the compound is an important intermediate for synthesizing JAK inhibitors for treating rheumatoid arthritis, namely ruxotinib and tofacitinib.
At present, the main method for synthesizing 4, 6-dichloropyrimidine-5-acetaldehyde is reported according to documents CN108409745A, CN103534257A, CN104230939A, WO03105770, WO2013138436, WO2010009207, WO2010009208, WO2011062885, Chemistry of Heterocyclic Compounds 2018,54(6), 638-642 and the like, wherein malonate is used as a raw material and reacts with 3-bromopropene to obtain an intermediate A, then formamidine is used for cyclization to obtain an intermediate B, the intermediate B is chlorinated to obtain an intermediate C, and finally the intermediate C is oxidized to obtain a target product 4, 6-dichloropyrimidine-5-acetaldehyde, wherein the reaction equation is as follows:
the main problem of the above method is the oxidation reaction in the last step, and it is known that potassium osmate or osmium tetroxide belong to inorganic drugs, and osmium tetroxide is extremely toxic and is not very beneficial to industrial production and environmental protection; although the ozonization reaction is economical and green and is suitable for industrial production, the ozonization reaction is also a very dangerous chemical reaction, has explosion risk when being operated improperly and needs ozone generator equipment, so the ozonization reaction is not suitable for the industrial large-scale production method.
At present, the two oxidation reactions adopt an intermittent process to produce the 4, 6-dichloropyrimidine-5-acetaldehyde, the state parameters such as the composition, the temperature and the like of materials (including intermediate products and final products) in a reactor in the operation process of the intermittent process can change along with time, the process is an unstable process, the production process and the product quality have great uncertainty, and the quality of downstream products is directly unstable and is difficult to control. The intermittent process for producing 4, 6-dichloropyrimidine-5-acetaldehyde has the following problems: 1. batch operation is inefficient and reaction times are long. 2. The traditional ozone oxidation production in the kettle needs lower temperature and has potential safety hazard.
In addition, the ozonization process belongs to the 10 th oxidation process in 18 dangerous processes which are intensively regulated and controlled by the government and has extremely high danger. The ozonization safety accidents are also often reported on the network, and the accidents are reported in the industry as ozone oxidation reactions. Therefore, a continuous synthesis process which is safe, simple to operate, efficient and easy to produce 4, 6-dichloropyrimidine-5-acetaldehyde on a large scale needs to be found.
Disclosure of Invention
The invention aims to solve the technical problems of low yield, high risk, low safety coefficient and inconvenience for industrial production in the intermittent process for producing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde, and aims to provide a process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation, solve the problems, and provide a brand-new process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by ozonization, which is safe, simple to operate, high in efficiency, easy for large-scale production.
The invention is realized by the following technical scheme:
a process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation comprises the following steps of dissolving a raw material C in a mixed solvent of methanol and dichloromethane, preparing a liquid material according to the mass ratio of the raw material C to the methanol to the dichloromethane of 1: 2-12: 0-10, introducing the liquid material into a precooler by using a metering pump according to the flow of 10-200 ml/min, precooling the liquid material to the reaction temperature of-60 ℃ to-20 ℃, precooling ozone according to the flow of 6-60L/min by using the precooler, introducing the precooled liquid material and the liquid material into a gas-liquid mixing reactor precooled to the reaction temperature of-60 ℃ to-20 ℃, allowing the liquid material to stay in the gas-liquid mixing reactor for 20s to 200s, allowing the liquid material to flow into a gas-liquid separator, performing reduction reaction on an aqueous solution prepared from separated reaction liquid and a reducing agent, extracting the solvent, drying, concentrating and recrystallizing to obtain a target product D, wherein the target product D is the chemical structural formula of the raw material C:
the invention takes 5-allyl-4, 6-dichloropyrimidine as a raw material, and obtains a target product by continuous flow ozonization and reduction by a reducing agent, and the 5-allyl-4, 6-dichloropyrimidine is taken as a raw material C. As a rapid and efficient full-flow continuous process, the continuous flow synthesis process has the characteristics of short time consumption, high efficiency, easy operation and the like, raw materials are continuously added in the process, products are continuously produced, materials (namely reaction mixtures containing the raw materials, intermediates, products, solvents and the like) continuously flow in the process, the reaction mixtures are not interrupted, the reaction mixtures do not stay for waiting, the products are continuously produced, and the process is a 'flow line' type chemical production process. When the process operation reaches a steady state, the state parameters of the composition, the temperature and the like of the materials at any position in the reactor do not change along with the time, and the process is a steady state process, so the production process and the product quality are stable; compared with the intermittent ozonization process operation, the invention has the following advantages: small equipment, short time, high efficiency, easy operation and the like, and the process is intrinsically safe.
According to the invention, the ozone and the liquid material can be sequentially subjected to precooling, gas-liquid mixing reactor and gas-liquid separator to obtain the reaction liquid rapidly, and the oxidation reaction liquid can rapidly enter the reduction system for reduction reaction without long-time retention. The residence time of the materials in each stage is short, further side reaction is avoided, the high yield of the product is ensured, the production efficiency is high, and full continuous flow synthesis of reaction and post-treatment is realized.
The step of introducing ozone into the gas-liquid mixing reactor comprises the following steps:
the ozone generating process comprises the following steps: the ozone generator is firstly filled with cooling water of the shell of the ozone generator, then the oxygen is switched on and adjusted to the required flow, then the power supply is switched on and adjusted to the required power, and the ozone generator generates ozone.
And introducing the generated ozone into a gas-liquid mixing reactor and reacting with the liquid material introduced into the gas-liquid mixing reactor at the same time, wherein the flow of the oxygen is 6-60L/min, and the electric power is 0.25-5.0 KW.
The high temperature is not beneficial to the generation of ozone but beneficial to the decomposition of the ozone, so that the yield and the concentration of the ozone are reduced, and cooling water of the shell of the ozone generator is used for heat dissipation; when the ozone is prepared, the parameter adjustment of the ozone generator is matched with the parameters of the continuous flow oxidation reaction.
Preferably, the oxygen sources used by the ozone generator are all steel cylinder oxygen.
Preferably, the reducing agent is one or more of sodium thiosulfate, thiourea, sodium metabisulfite or zinc powder.
Preferably, the extraction solvent is ethyl acetate or dichloromethane.
Preferably, the recrystallization solvent used for recrystallization is a mixture of ethyl acetate and petroleum ether, ethyl acetate: the mass ratio of the petroleum ether is 1: 1 to 10.
Preferably, the metering pump is one of a peristaltic pump, a diaphragm pump, a advection pump or a plunger pump.
Preferably, the gas-liquid mixing reactor is one of a venturi mixer, an SK mixer and a corning G1 mixer.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. the process for synthesizing the 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde by continuous flow ozone oxidation saves the production processes of a plurality of intermediates, is simple, can realize continuous flow synthesis, and has high production efficiency and simple operation;
2. the process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation adopts a continuous flow synthesis process, and when the process operation reaches a steady state, the state parameters of material composition, temperature and the like at any position in a reactor do not change along with time, and the process is a steady-state process, so that the production process and the product quality are stable.
Drawings
The accompanying drawings, which are included to provide a further understanding of the embodiments of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the principles of the invention. In the drawings:
FIG. 1 is a schematic flow chart of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples and accompanying drawings, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not meant to limit the present invention.
Example 1
As shown in figure 1, the process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation comprises the following steps of dissolving a raw material C in a mixed solvent of methanol and dichloromethane, preparing a liquid material according to the mass ratio of the raw material C, the methanol and the dichloromethane, of 1: 2-12: 0-10, introducing the liquid material into a precooler by using a metering pump according to the flow rate of 10-200 ml/min, precooling the liquid material to the reaction temperature of-60 ℃ to-20 ℃, introducing ozone into a gas-liquid mixing reactor precooled to the reaction temperature of-60 ℃ to-20 ℃ together with the liquid material according to the flow rate of 6-60L/min, staying the liquid material in the gas-liquid mixing reactor for 20s to 200s, flowing into a gas-liquid separator, carrying out reduction reaction on the separated reaction liquid and an aqueous solution prepared by a reducing agent, extracting the solvent, drying, concentrating and recrystallizing to obtain a target product D, wherein the target product D is the 4, 6-dichloropyrimidine-5-acetaldehyde, and the equation 1 is shown in the following reaction flow:
the step of introducing ozone into the gas-liquid mixing reactor comprises the following steps:
the ozone generating process comprises the following steps: the ozone generator is firstly filled with cooling water of the shell of the ozone generator, then the oxygen is switched on and adjusted to the required flow, then the power supply is switched on and adjusted to the required power, and the ozone generator generates ozone.
And introducing the generated ozone into a gas-liquid mixing reactor and reacting with the liquid material introduced into the gas-liquid mixing reactor at the same time, wherein the flow of the oxygen is 6-60L/min, and the electric power is 0.25-5.0 KW.
The high temperature is not beneficial to the generation of ozone but beneficial to the decomposition of the ozone, so that the yield and the concentration of the ozone are reduced, and cooling water of the shell of the ozone generator is used for heat dissipation.
Preferably, the oxygen sources used by the ozone generator are all steel cylinder oxygen.
Preferably, the reducing agent is one or more of sodium thiosulfate, thiourea, sodium metabisulfite or zinc powder.
Preferably, the extraction solvent is ethyl acetate or dichloromethane.
Preferably, the recrystallization solvent used for recrystallization is a mixture of ethyl acetate and petroleum ether, ethyl acetate: the mass ratio of the petroleum ether is 1: 1 to 10.
Preferably, the metering pump is one of a peristaltic pump, a diaphragm pump, a advection pump or a plunger pump.
Preferably, the gas-liquid mixing reactor is one of a Venturi mixer, an SK mixer and a Corning G1 mixer
Compared with the intermittent ozonization process operation, the invention has the following advantages: small equipment, short time, high efficiency, easy operation and the like, and the process is intrinsically safe.
Example 2
Based on example 1, the specific synthesis steps of this example are that 20 g of raw material C, 40 g of methanol and 200 g of dichloromethane are mixed and dissolved to be used as a liquid material, the liquid material is sequentially introduced into a precooler and a reaction mixer by a peristaltic pump at a flow rate of 15ml/min, ozone is sequentially introduced into the precooler and the reaction mixer by an ozone generator at the same time at an oxygen flow rate of 6L/min and an ozone discharge power of 0.35KW, the reaction temperature of the reaction mixer is-30 ℃, the reaction mixer is an SK mixer, the liquid material stays in the reaction mixer for 60S, the T L C detects that the raw material disappears, then flows into a gas-liquid separator, oxygen and reaction liquid are separated out by the gas-liquid separator, all the reaction liquid is collected and added into a solution prepared from 30 g of sodium thiosulfate and 60 g of water, the temperature is controlled to be 0-10 ℃ for 1 hour, potassium iodide paper for detecting the unchanged starch is used for detecting, the reaction is ended, a lower dichloromethane phase is separated, the lower dichloromethane phase is washed by salt water, an organicAdding 20 g of ethyl acetate, heating for dissolving, adding 40 g of petroleum ether to separate out solid, filtering the solid, and drying to obtain 12 g of light yellow crystalline solid, wherein the yield is 60 percent and is 50 percent higher than that of the product in the prior art; the GC purity of the product is 99.5 percent, and the hydrogen spectrum detection result is as follows:1HNMR(400MHz,DMSO-d6)9.74(s,1H),8.87(s,1H),4.23(s,2H))。
the above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (8)
1. A process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation is characterized by comprising the following steps of dissolving a raw material C in a mixed solvent of methanol and dichloromethane, preparing a liquid material according to the mass ratio of the raw material C to the methanol to the dichloromethane of 1: 2-12: 0-10, introducing the liquid material into a precooler by using a metering pump according to the flow rate of 10-200 ml/min, precooling the liquid material to the reaction temperature of-60 ℃ to-20 ℃, precooling ozone according to the flow rate of 6-60L/min, introducing the precooled ozone and the liquid material into a gas-liquid mixed reactor precooled to the reaction temperature of-60 ℃ to-20 ℃, allowing the liquid material to stay in the gas-liquid mixed reactor for 20s to 200s, flowing into a gas-liquid separator, carrying out reduction reaction on the separated reaction liquid and an aqueous solution prepared into a reducing agent, extracting the solvent, drying, concentrating and recrystallizing to obtain a target product D, wherein the target product D is the chemical structural formula of the 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde:
2. the process for synthesizing 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde by continuous flow ozone oxidation according to claim 1, wherein the ozone is introduced into the gas-liquid mixing reactor, the ozone generator is introduced with cooling water into the outer shell of the ozone generator, then oxygen is introduced and is adjusted to the required flow, then a power supply is connected and is adjusted to the required power, the ozone generator generates ozone, the generated ozone is introduced into the gas-liquid mixing reactor and reacts with a liquid material simultaneously introduced into the gas-liquid mixing reactor, the flow of the oxygen is 6-60L/min, and the electric power is 0.25-5.0 KW.
3. The process of claim 2, wherein the ozone generator uses a source of oxygen gas that is steel-filled.
4. The process of claim 1, wherein the reducing agent is one or more of sodium thiosulfate, thiourea, sodium metabisulfite or zinc powder.
5. The process of claim 1, wherein the extraction solvent is ethyl acetate or dichloromethane.
6. The process of continuous flow ozonation synthesis of 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde according to claim 1, wherein the recrystallization solvent used for recrystallization is a mixture of ethyl acetate and petroleum ether, the ratio of ethyl acetate: the mass ratio of the petroleum ether is 1: 1 to 10.
7. The process for the continuous flow ozonation synthesis of 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde according to claim 1, wherein the metering pump is one of a peristaltic pump, a diaphragm pump, an advection pump, or a plunger pump.
8. The process of claim 1, wherein the gas-liquid mixing reactor is one of a venturi mixer, an SK mixer, and a corning G1 mixer.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010352384.9A CN111454215B (en) | 2020-04-28 | 2020-04-28 | Process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010352384.9A CN111454215B (en) | 2020-04-28 | 2020-04-28 | Process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111454215A true CN111454215A (en) | 2020-07-28 |
CN111454215B CN111454215B (en) | 2023-07-07 |
Family
ID=71676560
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010352384.9A Active CN111454215B (en) | 2020-04-28 | 2020-04-28 | Process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111454215B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113387919A (en) * | 2021-06-08 | 2021-09-14 | 爱斯特(成都)生物制药股份有限公司 | Method for continuous flow synthesis of piperonyl formaldehyde |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1512984A (en) * | 2001-05-30 | 2004-07-14 | ����贻�ѧ��ҵ��ʽ���� | Process for preparation of quinoline carboldehyde |
WO2008077769A1 (en) * | 2006-12-20 | 2008-07-03 | Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg | Process for the safe ozonolysis of organic compounds in flammable solvents |
CN108409745A (en) * | 2018-04-09 | 2018-08-17 | 华东师范大学 | A kind of synthetic method of chloro- 7H- pyrrolo-es [2,3-d] pyrimidines of 4- |
CN108997324A (en) * | 2018-08-21 | 2018-12-14 | 南京欧信医药技术有限公司 | The preparation method of rosuvastain calcium intermediate |
-
2020
- 2020-04-28 CN CN202010352384.9A patent/CN111454215B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1512984A (en) * | 2001-05-30 | 2004-07-14 | ����贻�ѧ��ҵ��ʽ���� | Process for preparation of quinoline carboldehyde |
WO2008077769A1 (en) * | 2006-12-20 | 2008-07-03 | Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg | Process for the safe ozonolysis of organic compounds in flammable solvents |
CN108409745A (en) * | 2018-04-09 | 2018-08-17 | 华东师范大学 | A kind of synthetic method of chloro- 7H- pyrrolo-es [2,3-d] pyrimidines of 4- |
CN108997324A (en) * | 2018-08-21 | 2018-12-14 | 南京欧信医药技术有限公司 | The preparation method of rosuvastain calcium intermediate |
Non-Patent Citations (2)
Title |
---|
DANIEL M. BOWLES等: "Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT 》 * |
刘津等: "4-甲基烟腈衍生物的合成研究", 《解放军药学学报》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113387919A (en) * | 2021-06-08 | 2021-09-14 | 爱斯特(成都)生物制药股份有限公司 | Method for continuous flow synthesis of piperonyl formaldehyde |
Also Published As
Publication number | Publication date |
---|---|
CN111454215B (en) | 2023-07-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111560624B (en) | Method for continuously preparing isobenzofuran compounds by using microchannel reaction device | |
CN105085388A (en) | Synthesis method for sorafenib intermediate | |
CN110616439B (en) | Method for synthesizing 4-sulfonic acid substituted isoquinolone derivative through electrochemical oxidation | |
CN107235959A (en) | A kind of novel method for synthesizing for preparing cancer therapy drug Niraparib | |
CN111454215A (en) | Process for synthesizing 2- (4, 6-dichloropyrimidin-5-yl) acetaldehyde by continuous flow ozone oxidation | |
JP2024504897A (en) | Pyridine-pyrrole-ruthenium complex, its production method, and its application as a catalyst for producing hydrazine by exerting electrocatalytic action on ammonia oxidation | |
CN107235967A (en) | The synthesis technique of antineoplastic Tegafur | |
Ahmed et al. | Flow electrochemical cyclizations via amidyl radicals: easy access to cyclic ureas | |
CN103923087B (en) | A kind of preparation method of deuterium-labeled sitagliptin | |
CN114293210B (en) | Method for continuously electrosynthesis of benzopyran-4-ketone by using micro-reaction device | |
CN111892532A (en) | Method for synthesizing 3-Cl propionyl substituted heterocyclic compound containing N by using micro-reaction device | |
CN113493408A (en) | Preparation method of 2,3, 6-trichloropyridine | |
CN106632014A (en) | Preparation of 2-amino-5-chloropyridine | |
CN114524816A (en) | Preparation method of 7-iodopyrrolo [2,1-f ] [1,2,4] triazin-4-amine | |
CN112239871A (en) | Method for continuously preparing C-2 chloro-substituted quinoline by using electrochemical microchannel reaction device | |
CN110713442A (en) | Preparation method of o-nitrobenzaldehyde | |
CN111925317A (en) | Ropivacaine hydrochloride impurity and preparation method thereof | |
CN110894195A (en) | Novel preparation method of 2-thiopheneacetic acid | |
Cerra et al. | Isocyanide chemistry enabled by continuous flow technology | |
CN116162945B (en) | Method for continuously and electrically synthesizing canagliflozin intermediate by utilizing micro-reaction device | |
CN113336725B (en) | Epoxy chloropropane production process and device thereof | |
CN113979965B (en) | Continuous production method of 4, 5-dichloro-2-octyl-4-isothiazolin-3-ketone | |
CN104926660B (en) | The green synthesis method of a kind of trinitrophloroglucinol and application | |
CN103787858B (en) | Method for preparing 9-fluorenone through fluorene | |
CA2349194A1 (en) | Process for the preparation of monohalogenated 2-oxo-1,3-dioxolanes |
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 |