CN109021011A - A method of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester - Google Patents
A method of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester Download PDFInfo
- Publication number
- CN109021011A CN109021011A CN201810922734.3A CN201810922734A CN109021011A CN 109021011 A CN109021011 A CN 109021011A CN 201810922734 A CN201810922734 A CN 201810922734A CN 109021011 A CN109021011 A CN 109021011A
- Authority
- CN
- China
- Prior art keywords
- methylphosphonic acid
- tolysulfonyl oxygen
- acid diethylester
- synthesizing
- added dropwise
- 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.)
- Pending
Links
- WGQMNJYLZXTHIN-UHFFFAOYSA-N Cc(cc1)ccc1S(OCP(OC)(OC)=O)(=O)=O Chemical compound Cc(cc1)ccc1S(OCP(OC)(OC)=O)(=O)=O WGQMNJYLZXTHIN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4075—Esters with hydroxyalkyl compounds
Abstract
The invention discloses a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester, diethyl phosphite is added dropwise in 37% formalin and catalyst mixing, it is added dropwise, insulation reaction 2 hours, obtains reaction solution, solvent is put into reaction solution, acid binding agent is added dropwise under low temperature in paratoluensulfonyl chloride, and heat preservation 2 hours or so is added dropwise, extraction, washing, distillation, surplus materials is high-purity tolysulfonyl oxygen methylphosphonic acid diethylester.The method of the present invention solves the disadvantages of prior art moderate purity is low, and yield is not high, complex procedures, and post-processing bothers, and environmental protection pressure is big, unsuitable industrialization.
Description
Technical field
The present invention relates to medical synthesis technical fields, more particularly to a kind of synthesis tolysulfonyl oxygen methylphosphonic acid diethyl
The method of ester.
Background technique
Tolysulfonyl oxygen methylphosphonic acid diethylester is used for herbicide and fungicide, is as conjunction there are one important use
At the intermediate of ucleosides antiviral agent, for treating disease of viral infection tenofovir disoproxil fumarate intermediate.Document report
The synthesis technology of the tolysulfonyl oxygen methylphosphonic acid diethylester in road, actual product purity is not high, and yield is lower, and post-processing is multiple
Miscellaneous, waste water treatmentntrol difficult, production cost remains high.
Currently, tolysulfonyl oxygen methylphosphonic acid diethylester synthetic route is relatively simple, and under the action of catalyst, phosphorous acid
Addition reaction occurs for diethylester and paraformaldehyde, obtains methylol diethyl phosphate, is directly added into reaction solution to toluene sulphur
Acyl chlorides makees the hydrochloric acid in acid binding agent and generated with triethylamine, generates tolysulfonyl oxygen methylphosphonic acid diethylester.The synthetic method
Universal purity is not high, and yield is lower.Its chemical general formula is as follows:
The prior art is such as:
1. the desolate equal (preparation and Separation Research Shandong Light Ind College of tolysulfonyl oxygen methylphosphonic acid diethylester of king's generation
Report in the May, 2010 second phase of volume 24) solvent is made using toluene, triethylamine makees catalyst, diethyl phosphite and paraformaldehyde
Reaction 5 hours, obtains methylol diethyl phosphate, then carries out tosylation, triethylamine is added dropwise using low temperature, reaction 20 is small
When, it obtains that product purity is low, is purified using silica gel column chromatography, yield is relatively low, and overall time-consuming, not environmentally, troublesome in poeration, cost
It is too high, be not suitable for industrialized production.
2. (synthesising process research " Shandong medicine thing " 05 phase in 2005 of tolysulfonyl oxygen methylphosphonic acid diethylester such as Cai Xia
Authors' working unit: Medicine Industry Inst., Shandong Prov.) solvent made using toluene, triethylamine makees catalyst, diethyl phosphite and more
Polyformaldehyde reacts 4 hours, obtains methylol diethyl phosphate, and then low temperature is added dropwise triethylamine progress tosylation and obtains to first
Benzene sulfonyl oxygen methylphosphonic acid diethylester is crossed after filtering out triethylamine hydrochloride, and filtrate by washing, wash, then washes, and obtains by sodium carbonate
Product purity it is lower, and triethylamine hydrochloride recycling it is more troublesome, ammonia nitrogen in waste water is very high, can not be effectively treated, environmental protection pressure
Power is big, is not suitable for large-scale production.
3. (the name of patent application: tolysulfonyl oxygen methylphosphonic acid new production technology of diethyl, publication number such as Wu's small peak
CN101565433 reactant aqueous solution 2-4 hours of diethyl phosphite and paraformaldehyde) are used, then are extracted with dichloromethane, so
After distill to obtain methylol diethyl phosphate, then carry out tosylation again.Product purity is low for the method first step, and extraction adds
Distillation increases process, reduces efficiency, increases cost.
4. (the name of patent application: the synthetic method patent of invention of tolysulfonyl oxygen methylphosphonic acid diethylester such as Ma Yongxiang
Publication number CN105541910A) use isopropanol to make solvent, potassium carbonate makees catalyst, and diethyl phosphite is anti-with paraformaldehyde
It answers, then distills out isopropanol recovering and apply, distillation residue is methylol diethyl phosphate, is added methylene chloride as solvent, low
Temperature is lower to be added dropwise triethylamine progress tosylation, and be then dissolved in water triethylamine hydrochloride, branch vibration layer, is washed with water one
It is secondary, methylene chloride recovery is steamed, distillation residue is tolysulfonyl oxygen methylphosphonic acid diethylester.The method drawback
It is obvious that recycling design is wanted in first step distillation, energy consumption is high, and the time is long；Contain a large amount of triethylammonium salts hydrochlorates, place in second step waste water
It is very big to manage difficulty, is not suitable for large-scale industrial production.
Summary of the invention
The present invention provides a kind of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester aiming at above-mentioned defect
Method, solve prior art moderate purity it is low, yield is not high, complex procedures, post-processing trouble, environmental protection pressure is big, be not suitable for work
The disadvantages of industry.
A kind of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester technical solution of the invention is, including the following steps:
(1) formalin of 37-38% and catalyst mixing, are added dropwise diethyl phosphite, are added dropwise, insulation reaction
It 2 hours, obtains reaction solution and is directly used in the next step；
(2) solvent is put into the reaction solution that step (1) obtains, paratoluensulfonyl chloride is added dropwise acid binding agent under low temperature, drips
It Bi Baowen 2 hours or so, extracts, washes, distillation, surplus materials is high-purity tolysulfonyl oxygen methylphosphonic acid diethylester；
Chemical equation is as follows:
In step (1), the catalyst is potassium carbonate, and one of sodium carbonate, additional amount accounts for the matter of formalin
Amount percentage composition is 5-6%.
In step (1), the catalyst is sodium carbonate.
In step (1), the mass ratio of the diethyl phosphite and formalin are as follows: 120:100-110.
In step (1), insulation reaction temperature is 0-30 degree.
In step (2), the solvent is at least one of methylene chloride, toluene.
In step (2), the solvent is methylene chloride.
In step (2), the sodium hydrate aqueous solution that the acid binding agent is 30%, liquid alkaline reaction speed is fast, and side reaction is few,
It is cheap and easy to get, and what is generated is sodium chloride, relatively good processing.
In step (2), diethyl phosphite, the molar ratio of paratoluensulfonyl chloride and sodium hydroxide are as follows: 1:0.95:1.1-
1.2。
In step (2), the dropping temperature is 5-10 degree.
The invention has the benefit that the present invention has the advantage that with the prior art
(1) side reaction is few, easy to operate；
(2) product purity is high, reaches 99.0% or more；
(3) molar yield is high, reaches 85% or more, prior art is generally lower than 80%；
(4) process is short, and post-processing is simple, and the reaction time is short, high production efficiency；
(5) waste water benefit is managed, no ammonia nitrogen, simple triple effect evaporation, and environmental protection pressure is small；
(6) it is suitble to large-scale industrial production.
Specific embodiment:
For a better understanding of the present invention, below with specific example come the technical solution that the present invention will be described in detail, but this
Invention is not limited thereto.
Embodiment 1
In (1) 500 milliliter of three-necked flask, 50 gram 37% of formalin is added, 3.0 grams of sodium carbonate, is cooled to 0 DEG C,
60 grams of diethyl phosphite are added dropwise, process temperature is added dropwise and is maintained between 0-5 DEG C, adds within 2 hours, after adding, 2 DEG C of heat preservations 2 are small
When obtain reaction solution.Sample detection, diethyl phosphite 0.12% (are lower than 0.2%), and reaction is completed.
(2) it adds methylene chloride in above-mentioned reaction solution 100 milliliters, 78.7 grams of paratoluensulfonyl chloride, is cooled to 5 DEG C, is added dropwise
63.8 grams of 30% liquid alkaline, exothermic heat of reaction keep adding within 1 hour between 5-10 DEG C of dropping temperature, 10 DEG C of heat preservations 2 are added dropwise
Hour, sample detection, paratoluensulfonyl chloride 0.15% (being lower than 0.2%) reaction is completed, and static, layering, water layer adds 50 milliliter two
Chloromethanes extraction is primary, merges the bed of material, adds 100 milliliters of washings primary, branch vibration layer；Dichloromethane is recycled in the air-distillation of bed of material elder generation
Alkane, then decompression draws and does remaining methylene chloride, 115.1 grams of tolysulfonyl oxygen methylphosphonic acid diethylesters of residue, purity
99.3%, molar yield (in terms of paratoluensulfonyl chloride) 86.5%.
It examines and method for detecting purity is as follows:
1. liquid phase detects
2. Detection wavelength: 260nm
3. mobile phase: A) acetonitrile
B) 0.1% phosphate aqueous solution
C) A:B=55:45
4. taking appropriate amount of sample to be placed in 10 milliliters of volumetric flasks with flowing phased soln and diluting
5 sample volumes: 20ul
6. runing time: 30 minutes
7. calculation method: area normalization method calculates degree.
The final residue of the present invention and standard control, it is consistent that liquid phase detects appearance time, it was demonstrated that is tolysulfonyl oxygen
Methylphosphonic acid diethylester.
Embodiment 2
In (1) 500 milliliter of three-necked flask, 55 gram 37% of formalin is added, 3.0 grams of sodium carbonate, is cooled to 0 DEG C,
60 grams of diethyl phosphite are added dropwise, process temperature is added dropwise and is maintained between 0-5 DEG C, adds within 2 hours, after adding, 2 DEG C of heat preservations 2 are small
When obtain reaction solution.Sample detection, diethyl phosphite 0.11% (are lower than 0.2%), and reaction is completed.
(2) it adds methylene chloride in above-mentioned reaction solution 100 milliliters, 78.7 grams of paratoluensulfonyl chloride, is cooled to 5 DEG C, is added dropwise
63.8 grams of 30% liquid alkaline, exothermic heat of reaction keep adding within 1 hour between 5-10 DEG C of dropping temperature, 10 DEG C of heat preservations 2 are added dropwise
Hour, sample detection, paratoluensulfonyl chloride 0.13% (being lower than 0.2%) reaction is completed, and static, layering, water layer adds 50 milliliter two
Chloromethanes extraction is primary, merges the bed of material, adds 100 milliliters of washings primary, branch vibration layer；Dichloromethane is recycled in the air-distillation of bed of material elder generation
Alkane, then decompression draws and does remaining methylene chloride, 115.2 grams of tolysulfonyl oxygen methylphosphonic acid diethylesters of residue, purity
99.1%, molar yield (in terms of paratoluensulfonyl chloride) 86.5%.
Embodiment 3
1) in 500 milliliters of three-necked flasks, 50 gram 37% of formalin is added, 3.0 grams of potassium carbonate, is cooled to 0 DEG C, drop
Add 60 grams of diethyl phosphite, process temperature is added dropwise and is maintained between 0-5 DEG C, adds within 2 hours, after adding, 2 DEG C keep the temperature 2 hours
Obtain reaction solution.Sample detection, diethyl phosphite 0.09% (are lower than 0.2%), and reaction is completed.
(2) it adds methylene chloride in above-mentioned reaction solution 100 milliliters, 78.7 grams of paratoluensulfonyl chloride, is cooled to 5 DEG C, is added dropwise
63.8 grams of 30% liquid alkaline, exothermic heat of reaction keep adding within 1 hour between 5-10 DEG C of dropping temperature, 10 DEG C of heat preservations 2 are added dropwise
Hour, sample detection, paratoluensulfonyl chloride 0.18% (being lower than 0.2%) reaction is completed, and static, layering, water layer adds 50 milliliter two
Chloromethanes extraction is primary, merges the bed of material, adds 100 milliliters of washings primary, branch vibration layer；Dichloromethane is recycled in the air-distillation of bed of material elder generation
Alkane, then decompression draws and does remaining methylene chloride, 113.2 grams of tolysulfonyl oxygen methylphosphonic acid diethylesters of residue, purity
98.6%, molar yield (in terms of paratoluensulfonyl chloride) 85.1%.
Embodiment 4
1) in 500 milliliters of three-necked flasks, 50 gram 37% of formalin is added, 3.0 grams of potassium carbonate, is cooled to 0 DEG C, drop
Add 60 grams of diethyl phosphite, process temperature is added dropwise and is maintained between 0-5 DEG C, adds within 2 hours, after adding, 25 DEG C keep the temperature 2 hours
Obtain reaction solution.Sample detection, diethyl phosphite 0.03% (are lower than 0.2%), and reaction is completed.
(2) it adds methylene chloride in above-mentioned reaction solution 100 milliliters, 78.7 grams of paratoluensulfonyl chloride, is cooled to 5 DEG C, is added dropwise
63.8 grams of 30% liquid alkaline, exothermic heat of reaction keep adding within 1 hour between 5-10 DEG C of dropping temperature, 10 DEG C of heat preservations 2 are added dropwise
Hour, sample detection, paratoluensulfonyl chloride 0.18% (being lower than 0.2%) reaction is completed, and static, layering, water layer adds 50 milliliter two
Chloromethanes extraction is primary, merges the bed of material, adds 100 milliliters of washings primary, branch vibration layer；Dichloromethane is recycled in the air-distillation of bed of material elder generation
Alkane, then decompression draws and does remaining methylene chloride, 110.8 grams of tolysulfonyl oxygen methylphosphonic acid diethylesters of residue, purity
98.2%, molar yield (in terms of paratoluensulfonyl chloride) 83.3%.
Embodiment 5
1) in 500 milliliters of three-necked flasks, 50 gram 37% of formalin is added, 3.0 grams of sodium carbonate, is cooled to 0 DEG C, drop
Add 60 grams of diethyl phosphite, process temperature is added dropwise and is maintained between 0-5 DEG C, adds within 2 hours, after adding, 2 DEG C keep the temperature 2 hours
Obtain reaction solution.Sample detection, diethyl phosphite 0.12% (are lower than 0.2%), and reaction is completed.
(2) it adds methylene chloride in above-mentioned reaction solution 100 milliliters, 78.7 grams of paratoluensulfonyl chloride, is cooled to 5 DEG C, is added dropwise
69.5 grams of 30% liquid alkaline, exothermic heat of reaction keep adding within 1 hour between 5-10 DEG C of dropping temperature, 10 DEG C of heat preservations 2 are added dropwise
Hour, sample detection, paratoluensulfonyl chloride 0.15% (being lower than 0.2%) reaction is completed, and static, layering, water layer adds 50 milliliter two
Chloromethanes extraction is primary, merges the bed of material, adds 100 milliliters of washings primary, branch vibration layer；Dichloromethane is recycled in the air-distillation of bed of material elder generation
Alkane, then decompression draws and does remaining methylene chloride, 114.8 grams of tolysulfonyl oxygen methylphosphonic acid diethylesters of residue, purity
99.2%, molar yield (in terms of paratoluensulfonyl chloride) 86.3%.
Embodiment 6
1) in 500 milliliters of three-necked flasks, 50 gram 37% of formalin is added, 3.0 grams of sodium carbonate, is cooled to 0 DEG C, drop
Add 60 grams of diethyl phosphite, process temperature is added dropwise and is maintained between 0-5 DEG C, adds within 2 hours, after adding, 2 DEG C keep the temperature 2 hours
Obtain reaction solution.Sample detection, diethyl phosphite 0.12% (are lower than 0.2%), and reaction is completed.
(2) add 100 milliliters of toluene in above-mentioned reaction solution, 78.7 grams of paratoluensulfonyl chloride, be cooled to 5 DEG C, be added dropwise 30%
63.8 grams of liquid alkaline, exothermic heat of reaction keeps adding within 1 hour between 5-10 DEG C of dropping temperature, is added dropwise 10 DEG C and keeps the temperature 2 hours, take
Sample detection, paratoluensulfonyl chloride 0.15% (being lower than 0.2%) reaction are completed, and static, layering, water layer adds 50 milliliters of toluene extractions one
It is secondary, merge the bed of material, adds 100 milliliters of washings primary, branch vibration layer；Methylene chloride is recycled in the air-distillation of bed of material elder generation, and then decompression is drawn
Do remaining methylene chloride, 115.2 grams of tolysulfonyl oxygen methylphosphonic acid diethylesters of residue, purity 99.1%, molar yield
(in terms of paratoluensulfonyl chloride) 86.5%.
Embodiment 7
Industrialized production
200 kilograms of formalin of investment 37% in (1) 1000 liter of reaction kettle, 12.0 kilograms of potassium carbonate, starting stirring,
It opens brine ice and is cooled to 0 DEG C, start to be added dropwise 240 kilograms of diethyl phosphite, kept for 0-5 DEG C of dropping temperature, 2 DEG C of left sides are added dropwise
Right heat preservation 2 hours, sample detection diethyl phosphite 0.15%, end of reaction stop stirring.It is spare
(2) upper step reaction solution is transferred in 2000 liters of reaction kettles, is pumped into 400 liters of methylene chloride, put into paratoluensulfonyl chloride
It 315 kilograms, opens brine ice and is cooled to 5 DEG C, start to be added dropwise 255 kilograms of liquid alkaline of 30%, kept for 5-10 DEG C of dropping temperature and dripped
Finish, add within 1 hour or so, be added dropwise, 10 DEG C or so keep the temperature 2 hours, and sample detection, paratoluensulfonyl chloride 0.14% (is lower than
0.2%) reaction is completed, static, layering, and water layer adds 400 liters of methylene chloride extractions primary, and branch vibration layer merges the bed of material, adds 400
Kilogram washing is primary, branch vibration layer；Methylene chloride is recycled in the air-distillation of bed of material elder generation, and then decompression draws and does remaining methylene chloride,
Distillation finishes, and is cooled to room temperature, and feed liquid puts bucket and weighs to obtain 460.2 kilograms of finished product in kettle.Colourless transparent liquid, through detecting purity
99.2%.
Claims (10)
1. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester, characterized in that it comprises the following steps:
(1) synthesis of methylol diethyl phosphate: phosphorous acid diethyl is added dropwise in formalin and the catalyst mixing of 37-38%
Ester is added dropwise, and insulation reaction 2 hours, obtains reaction solution and is directly used in the next step；
(2) solvent, paratoluensulfonyl chloride are put into the reaction solution that step (1) obtains, and acid binding agent is added dropwise under low temperature, guarantor is added dropwise
Temperature 2 hours or so extracts, and washes, and distillation, surplus materials is high-purity tolysulfonyl oxygen methylphosphonic acid diethylester；
Chemical equation is as follows:
2. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, which is characterized in that
In step (1), the catalyst is potassium carbonate, and one of sodium carbonate, the quality percentage that additional amount accounts for formalin contains
Amount is 5-6%.
3. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, which is characterized in that
In step (1), the catalyst is sodium carbonate.
4. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, which is characterized in that
In step (1), the mass ratio of the diethyl phosphite and formalin are as follows: 120:100-110.
5. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, which is characterized in that
In step (1), insulation reaction temperature is 0-30 degree.
6. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, which is characterized in that
In step (2), the solvent is at least one of methylene chloride, toluene.
7. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, which is characterized in that
In step (2), the solvent is methylene chloride.
8. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, which is characterized in that
In step (2), the acid binding agent be 30% sodium hydrate aqueous solution.
9. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 8, which is characterized in that
In step (2), diethyl phosphite, the molar ratio of paratoluensulfonyl chloride and sodium hydroxide are as follows: 1:0.95:1.1-1.2.
10. a kind of method for synthesizing tolysulfonyl oxygen methylphosphonic acid diethylester according to claim 1, feature exist
In in step (2), the dropping temperature is 5-10 degree.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810922734.3A CN109021011A (en) | 2018-08-14 | 2018-08-14 | A method of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810922734.3A CN109021011A (en) | 2018-08-14 | 2018-08-14 | A method of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109021011A true CN109021011A (en) | 2018-12-18 |
Family
ID=64634126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810922734.3A Pending CN109021011A (en) | 2018-08-14 | 2018-08-14 | A method of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109021011A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113121596A (en) * | 2021-04-22 | 2021-07-16 | 济南立德医药技术有限公司 | Preparation method of diethyl p-toluenesulfonyloxymethylphosphonate |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006003295A1 (en) * | 2004-06-09 | 2006-01-12 | Rhodia Chimie | Method for hydroxymethylation of a phosphonic acid in an esterified form |
| CN101020693A (en) * | 2007-02-05 | 2007-08-22 | 安徽师范大学 | Prepn process of Adefovir |
| CN101565433A (en) * | 2008-04-22 | 2009-10-28 | 吴小峰 | New production technology of diethyl (tosyloxy)methylphosphonate |
| CN101607971A (en) * | 2008-06-18 | 2009-12-23 | 天津天士力集团有限公司 | 9-[2-(diethoxy phosphonium mesitoyl methoxyl group) ethyl] synthetic method of VITAMIN B4 |
| CN102108086A (en) * | 2009-12-25 | 2011-06-29 | 中国人民解放军军事医学科学院微生物流行病研究所 | Method for preparing p-tosyloxymethyl diethyl phosphonate |
| CN103073747A (en) * | 2012-12-18 | 2013-05-01 | 江苏雅克科技股份有限公司 | Phosphorus-containing fire retardant and its preparation method |
| US20140046085A1 (en) * | 2010-08-31 | 2014-02-13 | Chimerix, Inc. | Phosphonate Ester Derivatives and Methods of Synthesis Thereof |
| CN204933466U (en) * | 2015-09-10 | 2016-01-06 | 山东沾化永浩医药科技有限公司 | A kind of synthesis reaction vessel of tolysulfonyl oxygen methylphosphonic acid diethylester |
| CN106699814A (en) * | 2017-02-04 | 2017-05-24 | 辰欣药业股份有限公司 | Preparation method of adefovir dipivoxil crystals |
| CN107021985A (en) * | 2017-05-08 | 2017-08-08 | 四川理工学院 | The synthetic method of pharmaceutical intermediate R 9 [2 (diethylphosphono methoxyl) propyl group] adenine |
-
2018
- 2018-08-14 CN CN201810922734.3A patent/CN109021011A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006003295A1 (en) * | 2004-06-09 | 2006-01-12 | Rhodia Chimie | Method for hydroxymethylation of a phosphonic acid in an esterified form |
| CN101020693A (en) * | 2007-02-05 | 2007-08-22 | 安徽师范大学 | Prepn process of Adefovir |
| CN101565433A (en) * | 2008-04-22 | 2009-10-28 | 吴小峰 | New production technology of diethyl (tosyloxy)methylphosphonate |
| CN101607971A (en) * | 2008-06-18 | 2009-12-23 | 天津天士力集团有限公司 | 9-[2-(diethoxy phosphonium mesitoyl methoxyl group) ethyl] synthetic method of VITAMIN B4 |
| CN102108086A (en) * | 2009-12-25 | 2011-06-29 | 中国人民解放军军事医学科学院微生物流行病研究所 | Method for preparing p-tosyloxymethyl diethyl phosphonate |
| US20140046085A1 (en) * | 2010-08-31 | 2014-02-13 | Chimerix, Inc. | Phosphonate Ester Derivatives and Methods of Synthesis Thereof |
| CN103073747A (en) * | 2012-12-18 | 2013-05-01 | 江苏雅克科技股份有限公司 | Phosphorus-containing fire retardant and its preparation method |
| CN204933466U (en) * | 2015-09-10 | 2016-01-06 | 山东沾化永浩医药科技有限公司 | A kind of synthesis reaction vessel of tolysulfonyl oxygen methylphosphonic acid diethylester |
| CN106699814A (en) * | 2017-02-04 | 2017-05-24 | 辰欣药业股份有限公司 | Preparation method of adefovir dipivoxil crystals |
| CN107021985A (en) * | 2017-05-08 | 2017-08-08 | 四川理工学院 | The synthetic method of pharmaceutical intermediate R 9 [2 (diethylphosphono methoxyl) propyl group] adenine |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113121596A (en) * | 2021-04-22 | 2021-07-16 | 济南立德医药技术有限公司 | Preparation method of diethyl p-toluenesulfonyloxymethylphosphonate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105367557A (en) | Method for preparing cycloxylidin | |
| CN110452136A (en) | A method of preparing taurine | |
| JP5296063B2 (en) | Method for producing a ruthenium complex | |
| CN111574470B (en) | Synthesis method of metamifop | |
| CN105541844B (en) | Simple preparation method of high-purity linagliptin | |
| EP3915981B1 (en) | Method for preparation of efinaconazole in ionic liquid medium | |
| CN109021011A (en) | A method of synthesis tolysulfonyl oxygen methylphosphonic acid diethylester | |
| CN102399238A (en) | Preparation method for amifostine | |
| CN103788010B (en) | Febuxostat intermediate and preparation method thereof | |
| CN102712593A (en) | Method for producing 2-amino-4-(trifluoromethyl)pyridine | |
| CN106565531A (en) | Synthesis method for pharmaceutically acceptable salt of alkylhydrazine | |
| CN110452089A (en) | The synthetic method of p-chloromethyl styrene | |
| US2945038A (en) | 5-fluorocytosine and preparation thereof | |
| CN101781250A (en) | Method for synthesizing low bromine content iminazole ionic liquid | |
| CN105481797B (en) | A kind of synthetic method of moroxydine hydrochlofide | |
| CN105175294B (en) | Method for synthesizing sulfanilamide by using chlorobenzene as raw material | |
| CN111925333A (en) | Preparation method, product and application of 2-amino-5-methylpyrazine | |
| CN106478495A (en) | Functionalized ion liquid and its synthetic method for lithium extraction | |
| JP5896521B2 (en) | Method for producing 2,2-dimethylpropanethioamide | |
| CN102557917A (en) | Method for preparing 2,4,6-trimethylphenylacetic acid | |
| CN105440074A (en) | Recycling method for mother liquor of N-(phosphonomethyl)iminodiacetic acid | |
| CN112759563B (en) | Preparation method of 1-cyclohexyl-2- (morpholinoethyl) carbodiimide methyl p-toluenesulfonate | |
| CN105503671A (en) | Preparation method of p-toluene sulfonyl chloride | |
| CN115572262A (en) | Isoquinoline derivative and preparation method thereof | |
| CN112110800B (en) | 3-aryl-2-propyne-1-alcohol derivative and preparation method thereof |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181218 |
|
| RJ01 | Rejection of invention patent application after publication |