CN101671238B - Preparation method of 2-bromoethyl methyl ether - Google Patents

Preparation method of 2-bromoethyl methyl ether Download PDF

Info

Publication number
CN101671238B
CN101671238B CN2009101530112A CN200910153011A CN101671238B CN 101671238 B CN101671238 B CN 101671238B CN 2009101530112 A CN2009101530112 A CN 2009101530112A CN 200910153011 A CN200910153011 A CN 200910153011A CN 101671238 B CN101671238 B CN 101671238B
Authority
CN
China
Prior art keywords
preparation
solvent
boric acid
reaction
metaboric
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.)
Active
Application number
CN2009101530112A
Other languages
Chinese (zh)
Other versions
CN101671238A (en
Inventor
瞿军
沈润溥
陆文辉
龚志娟
张符
吴宏祥
时立
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yangzhou Prince Pharmaceutical Technology Co ltd
University of Shaoxing
Original Assignee
YANGZHOU PRINCECHEM CO Ltd
University of Shaoxing
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by YANGZHOU PRINCECHEM CO Ltd, University of Shaoxing filed Critical YANGZHOU PRINCECHEM CO Ltd
Priority to CN2009101530112A priority Critical patent/CN101671238B/en
Publication of CN101671238A publication Critical patent/CN101671238A/en
Application granted granted Critical
Publication of CN101671238B publication Critical patent/CN101671238B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明公开了一种医药化工的重要中间体2-溴乙基甲基醚的制备方法。现有的各种方法或收率低，或原料制备困难，都不太适用于工业化生产。本发明采用的技术方案为：2溴乙基甲基醚的制备方法，以2-甲氧基乙醇为原料，首先在溶剂存在下与偏硼酸酐反应得到偏硼酸三-(2-甲氧基-1-基)-乙酯，然后将得到的中间体偏硼酸三-(2-甲氧基-1-基)-乙酯用溴化氢处理得到目标产物2-溴乙基甲基醚。本发明的反应易操作，体系温和，副反应少，产品的含量和收率高；硼酸等能回收套用，反应产生的污染物少。The invention discloses a preparation method of 2-bromoethyl methyl ether, an important intermediate of medicine and chemical industry. The various existing methods have low yields or difficulties in raw material preparation, and are not suitable for industrial production. The technical scheme adopted in the present invention is: the preparation method of 2-bromoethyl methyl ether, using 2-methoxyethanol as raw material, firstly reacting with metaboric anhydride in the presence of a solvent to obtain metaboric acid tri-(2-methoxy -1-yl)-ethyl ester, and then the obtained intermediate tris-(2-methoxy-1-yl)-ethyl metaborate is treated with hydrogen bromide to obtain the target product 2-bromoethyl methyl ether. The reaction of the invention is easy to operate, the system is mild, the side reaction is less, the content and yield of the product are high; the boric acid and the like can be recycled and used mechanically, and the reaction produces less pollutants.

Description

The preparation method of 2-bromo-ethyl-methyl ether
Technical field
The present invention relates to chemical field, specifically a kind of preparation method of important intermediate 2-bromo-ethyl-methyl ether of medication chemistry.
Background technology
The 2-bromo-ethyl-methyl ether is the important intermediate of medication chemistry, like the midbody as the anticarcinogen Tarceva.Its compound method mainly contains following several kinds:
Direct and the phosphorus tribromide prepared in reaction of A:2-methyl cellosolve, synthetic route is following:
CH 3OCH 2CH 2OH+PBr 3→CH 3OCH 2CH 2Br，
This method is the most frequently used method, and is simple and direct; But yield low (usually less than 50%) is difficult to obtain finished product, and cost is high.
B: carry out the substitution reaction preparation by 2-chloroethyl methyl ether and bromizating agent, synthetic route is following:
Figure G2009101530112D00011
Problems such as also there is the aftertreatment difficulty in this method, and yield is low.
C: methyl alcohol, bromine and activatory iron tetracarbonyl ethene complex compound prepared in reaction, synthetic route is following:
CH 3OH+(CH 2＝CH)-Fe(CO) 4+Br 2→CH 3OCH 2CH 2Br，
This method rests on theoretical research stage at present, is inappropriate for industrial production.
D: with tricresyl phosphite (2-methoxyl group-1-ethyl-) ester is that raw material carries out the bromination reaction preparation, and synthetic route is following:
Figure G2009101530112D00012
This method feedstock production difficulty is inappropriate for industrial production.
Above-mentioned each method or yield are low, or the feedstock production difficulty, all not too are applicable to suitability for industrialized production.
Summary of the invention
Technical problem to be solved by this invention is to overcome the defective that above-mentioned prior art exists, and a kind of novel method of the 2-of preparation bromo-ethyl-methyl ether is provided, and to improve the content and the yield of product, reduces and pollutes, and is fit to suitability for industrialized production.
For this reason; The present invention adopts following technical scheme: the preparation method of 2-bromo-ethyl-methyl ether; With the 2-methyl cellosolve is raw material; At first in the presence of solvent, obtain metaboric acid three-(2-methoxyl group-1-yl)-ethyl ester, the midbody metaboric acid three that obtains-(2-methoxyl group-1-yl)-ethyl ester is handled obtaining title product 2-bromo-ethyl-methyl ether then with hydrogen bromide with the metaboric acid anhydride reactant.
The metaboric acid acid anhydride is the raw material on-site prepn by boric acid, and reaction formula is:
Figure G2009101530112D00021
Be reflected under 70-130 ℃ and carry out, usually with boiling spread at 70-130 ℃ and exist refluxed to react with the immiscible solvent of water, aromatic hydrocarbons or esters solvents such as ETHYLE ACETATE, butylacetate such as solvent commonly used such as benzene,toluene,xylene; The mode that is adopted is an azeotropic band water, and the general reaction times is 1.5-4.5 hour, till water is no longer taken out of; Used quantity of solvent is generally 3-6 times of boric acid, does not have special restriction.
The metaboric acid acid anhydride that obtains is usually without separation; Directly in solvent, carry out next step reaction, finish the back like band water and add 2-methyl cellosolve, band water to the reaction solution that continues to reflux is transparent; No longer till the water outlet, just can obtain corresponding metaboric acid three-(2-methoxyl group-1-yl)-ethyl ester; Synthetic route is following:
Figure G2009101530112D00022
Also can adopt boric acid, 2-methyl cellosolve and solvent the reflux mode of band water of back that feeds intake is together reacted.
Described 2-methyl cellosolve charging capacity is 1 to 1.5 times (mole) of boric acid, with 1.1-1.2 doubly better, carries out next step reaction after can after reaction finishes, steaming solvent and excessive 2-methyl cellosolve, also can directly carry out next step reaction.The activity of midbody metaboric acid three-(2-methoxyl group-1-yl)-ethyl ester is very high, is easy to take place reactions such as hydrolysis and nucleophilic substitution, and the present invention has utilized the high characteristics of its reactive behavior to accomplish novel process.
The mol ratio of hydrogen bromide and boric acid is 1.0-1.5: 1 is better, and with 1.1-1.2: 1 is best.Hydrogen bromide can use pure bromize hydrogen gas to feed; Also can use the solution of hydrogen bromide in inert solvent; All right on-the-spot in-situ preparing adds Sodium Bromide or other method etc. as adopting sulfuric acid.The decomposition reaction of midbody metaboric acid ester is following:
Figure G2009101530112D00031
It is that methylene dichloride, chloroform or toluene, benzene etc. are to sour inert solvent that hydrogen bromide decomposes the used solvent of midbody metaboric acid ester reaction.Described temperature of reaction is-5 ℃ to 40 ℃, with 15-30 ℃ better; Temperature is high to be prone to produce side reaction, and temperature crosses that low that speed of response is slowed down is also not too favourable.
Decompose in the midbody metaboric acid ester process at hydrogen bromide; Usually boric acid derivatives can constantly be separated out as by product; Its solubleness in organic solvent is low; Therefore can add less water earlier after reaction finishes boric acid derivatives is converted into boric acid, the boric acid of filtered and recycled can be applied mechanically after with the solvent rinsing, promptly reduces pollution and reducing cost again; Filtrating directly adds washing, layering, wash neutrality with sodium bicarbonate aqueous solution again after, layering, rectifying just can obtain pure product 2-bromo-ethyl-methyl ether after organic layer reclaimed solvent.
The present invention has following beneficial effect: reaction raw materials 2-methyl cellosolve, boric acid, hydrogen bromide etc. all are large industrial raw material, and be cheap and easy to get; React easy to operate, system is gentle, and side reaction is few, and the content of product and yield are high; Ability such as boric acid recovery set usefulness, the pollutent that reaction produces is few.
Below in conjunction with embodiment the present invention is described further.
Embodiment
Analytical instrument of using among the embodiment and equipment: gas chromatography mass spectrometry, MS5973N-GC6890N (U.S. Agilent company); NMR, AVANCE DMX II I 400M (mark in the TMS, Bruker company); IR, NICOLET 360FT-IR; Gc: the beautiful 7890F in sky, Shanghai.
The preparation of embodiment 1:2-bromo-ethyl-methyl ether
In the 500ml there-necked flask, add boric acid 84g (1.4mol), toluene 260ml, band water refluxes; Synteny goes out 23.5g water (1.3mol) after about 2 hours, cools to 90 ℃, adds 2-methyl cellosolve 122g (1.6mol), and the band water 4 hours of continuing to reflux is transparent to reaction solution; No longer till the water outlet, lower the temperature water pump decompression and solvent recovery toluene and unreacted 2-methyl cellosolve; Get colourless transparent liquid 173g, be midbody metaboric acid three-(2-methoxyl group-1-yl)-ethyl ester, structural confirmation:
1HNMR(400MHz，CDCl 3)δ(ppm)：3.38(s，3H，O-CH 3)；3.54(t，J＝4.8Hz，2H，B-O-CH 2CH* 2-O-CH 3)；4.09(s，2H，B-O-CH* 2CH 2-O-CH 3)
13CNMR(400MHz，CDCl 3)δ(ppm)：58.94(O-CH 3)；63.32(B-O-CH* 2CH 2-O-CH 3)；72.38(B-O-CH 2CH* 2-O-CH 3)。
In above-mentioned liquid residue, add chloroform 200ml, down slowly logical bromize hydrogen gas 130g (1.6mol, available weightening finish method metering) is stirred in the cooling bath insulation, needs led in 4 hours approximately, continues to stir half a hour, is added dropwise to (the careful heat release of 30 ml waters then! ), stirring 10 minutes after-filtration, filter residue is washed with 50ml chloroform bubble, dries to such an extent that white solid boric acid 77 restrains, and can apply mechanically.Filtrating merges back water 50ml and washes layering; Wash more than the neutrality with sodium bicarbonate aqueous solution again, anhydrous magnesium sulfate drying, decompression and solvent recovery is to doing then, and the cut of collecting 107-110 ℃ gets product 153 grams, is colourless liquid, places flavescence, gas phase content 98.1%, total recovery 78.3% (calculating with boric acid).
Product structure is confirmed:
GC-MS(m/e)：45(100％)，63，94，96，107，109，138，140；
1HNMR(400MHz，CDCl 3)δ(ppm)：3.17(s，3H，O-CH 3)；3.41(t，J＝7.2Hz，2H，BrC*H 2CH 2-O-CH 3)；3.53(t，J＝7.2Hz，2H，BrCH 2C*H 2-O-CH 3)
13CNMR(400MHz，CDCl 3)δ(ppm)：30.72(BrC*H 2CH 2-O-CH 3)；56.94(O-CH 3)；73.12(BrCH 2C*H 2-O-CH 3)
IR(v/cm -1)：2812-2986(C-H)，1125(CH 2-O-CH 2)。
The preparation of embodiment 2:2-bromo-ethyl-methyl ether
In the 500ml there-necked flask, add the boric acid 77g (1.4mol) that reclaims among new boric acid 7g and the embodiment 1, the toluene and the 2-methyl cellosolve mixed solution 240ml that reclaim among the embodiment 1; New 2-methyl cellosolve 107g (1.4mol) refluxes and is with water, and synteny goes out 50g water after about 5 hours, cools to 20 ℃; Down slowly logical bromize hydrogen gas 130g (1.6mol, available weightening finish method metering) is stirred in the cooling bath insulation; Needed led in 4 hours approximately, continue to stir half a hour, be added dropwise to (the careful heat release of 30 ml waters then! ), stirring 10 minutes after-filtration, filter residue is washed with 50ml toluene bubble, dries to such an extent that white solid boric acid 78 restrains, and can apply mechanically.Filtrating merges back water 50ml and washes layering; Wash more than the neutrality with sodium bicarbonate aqueous solution again, anhydrous magnesium sulfate drying, decompression and solvent recovery is to doing then, and the cut of collecting 107-110 ℃ gets product 156 grams, is light yellow liquid, gas phase content 98.3%, total recovery 80% (calculating with boric acid).The product nuclear magnetic spectrogram is identical with embodiment 1.
The preparation of embodiment 3:2-bromo-ethyl-methyl ether
In the 500ml there-necked flask, add the boric acid 78g (1.4mol) that reclaims among new boric acid 6g and the embodiment 2, benzene 260ml, band water refluxes; Synteny goes out 23.7g water (1.3mol) after about 2 hours, cools to 90 ℃, adds 2-methyl cellosolve 122g (1.6mol); The band water 4 hours of continue refluxing is transparent to reaction solution, no longer till the water outlet, and cooling; Water pump decompression and solvent recovery benzene and unreacted 2-methyl cellosolve get colourless transparent liquid 171g, and 250ml adds methylene chloride in above-mentioned liquid residue; Down slowly logical bromize hydrogen gas 130g (1.6mol, available weightening finish method metering) is stirred in the cooling bath insulation; Needed led in 4 hours approximately, continue to stir half a hour, be added dropwise to (the careful heat release of 30 ml waters then! ), stirring 10 minutes after-filtration, filter residue is washed with 50ml chloroform bubble, dries to such an extent that white solid boric acid 77.5 restrains, and can apply mechanically.Filtrating merges back water 50ml and washes layering; Wash more than the neutrality with sodium bicarbonate aqueous solution again, anhydrous magnesium sulfate drying, decompression and solvent recovery is to doing then, and the cut of collecting 107-110 ℃ gets product 145 grams, is colourless liquid, gas phase content 97.9%, total recovery 74.1% (calculating with boric acid).
The preparation of embodiment 4:2-bromo-ethyl-methyl ether
Band water solvent among the embodiment 1 is changed to ETHYLE ACETATE, and other charge ratio is identical with reaction conditions, behind water pump decompression and solvent recovery ETHYLE ACETATE and the unreacted 2-methyl cellosolve, gets colourless transparent liquid 170g; Transfer in the 1000ml there-necked flask after in above-mentioned liquid residue, adding chloroform 250ml dissolving; Add Sodium Bromide 165g (1.6mol); The cooling bath insulation slowly drips vitriol oil 80g (0.8mol) under the mechanical stirring, needed drip off in 3 hours approximately; Continue to stir half a hour, be added dropwise to (the careful heat release of 50 ml waters then! ), stir 10 minutes after-filtration.Filtrate water 50ml washes, layering; Wash more than the neutrality with sodium bicarbonate aqueous solution again, anhydrous magnesium sulfate drying, decompression and solvent recovery is to doing then, and the cut of collecting 107-110 ℃ gets product 137 grams, is light yellow liquid, gas phase content 98.2%, total recovery 70.1% (calculating with boric acid).
The preparation of embodiment 5:2-bromo-ethyl-methyl ether
Band water solvent among the embodiment 1 is changed to butylacetate, and other charge ratio is identical with reaction conditions, behind water pump decompression and solvent recovery ETHYLE ACETATE and the unreacted 2-methyl cellosolve, gets colourless transparent liquid 174g; Transfer in the 1000ml there-necked flask after the 300ml that in above-mentioned liquid residue, the adds methylene chloride dissolving; Add Sodium Bromide 165g (1.6mol); The cooling bath insulation slowly drips vitriol oil 80g (0.8mol) under the mechanical stirring, needed drip off in 3 hours approximately; Continue to stir half a hour, be added dropwise to (the careful heat release of 50 ml waters then! ), stir 10 minutes after-filtration.Filtrate water 50ml washes, layering; Wash more than the neutrality with sodium bicarbonate aqueous solution again, anhydrous magnesium sulfate drying, decompression and solvent recovery is to doing then, and the cut of collecting 107-110 ℃ gets product 141 grams, is light yellow liquid, gas phase content 98.2%, total recovery 72.2% (calculating with boric acid).

Claims (6)

1.2-溴乙基甲基醚的制备方法，以2-甲氧基乙醇为原料，首先在溶剂存在下与偏硼酸酐反应得到偏硼酸三-(2-甲氧基-1-基)-乙酯，然后将得到的中间体偏硼酸三-(2-甲氧基-1-基)-乙酯用溴化氢处理得到目标产物2-溴乙基甲基醚；1. The preparation method of 2-bromoethyl methyl ether, with 2-methoxyethanol as raw material, first reacts with metaboric anhydride in the presence of a solvent to obtain metaboric acid tris-(2-methoxyl-1-yl)-ethyl ester, and then the obtained intermediate tris-(2-methoxy-1-yl)-ethyl metaborate is treated with hydrogen bromide to obtain the target product 2-bromoethyl methyl ether; 所述的偏硼酸酐由硼酸为原料脱水制得，反应在70-130℃下进行，在沸点范围为70-130℃且与水不互溶的溶剂存在下进行回流反应，所采用的方式为共沸带水，带水结束后得到的偏硼酸酐与溶剂不分离，直接在溶剂中加入2-甲氧基乙醇进行酯化反应。The metaboric anhydride is prepared by dehydration of boric acid as a raw material, the reaction is carried out at 70-130°C, and the reflux reaction is carried out in the presence of a solvent with a boiling point range of 70-130°C and is immiscible with water. Boiling with water, the metaboric anhydride obtained after the end of the water is not separated from the solvent, and 2-methoxyethanol is directly added to the solvent for esterification. 2.根据权利要求1所述的制备方法，其特征在于2-甲氧基乙醇与偏硼酸酐进行酯化反应时，所述的2-甲氧基乙醇摩尔用量为硼酸摩尔用量的1-1.5倍，在酯化反应结束后不分离直接进行下一步分解反应。2. preparation method according to claim 1, is characterized in that when 2-methoxyethanol and metaboric anhydride carry out esterification reaction, described 2-methoxyethanol molar dosage is 1-1.5 of boric acid molar dosage times, after the end of the esterification reaction, the next decomposition reaction is directly carried out without separation. 3.根据权利要求2所述的制备方法，其特征在于2-甲氧基乙醇与偏硼酸酐进行酯化反应时，所述的2-甲氧基乙醇摩尔用量为硼酸摩尔用量的1.1-1.2倍。3. preparation method according to claim 2, it is characterized in that when 2-methoxyethanol and metaboric anhydride carry out esterification reaction, described 2-methoxyethanol molar dosage is 1.1-1.2 of boric acid molar dosage times. 4.根据权利要求1所述的制备方法，其特征在于酯化反应所用的溶剂为苯、甲苯、二甲苯、乙酸乙酯或乙酸丁酯。4. preparation method according to claim 1 is characterized in that the used solvent of esterification is benzene, toluene, xylene, ethyl acetate or butyl acetate. 5.根据权利要求1所述的制备方法，其特征在于溴化氢分解反应所用的溶剂为二氯甲烷、氯仿、甲苯或苯。5. preparation method according to claim 1 is characterized in that the used solvent of hydrogen bromide decomposition reaction is methylene dichloride, chloroform, toluene or benzene. 6.根据权利要求1所述的制备方法，其特征在于分解反应结束后先加水将产生的硼酸衍生物转化为硼酸，过滤回收的硼酸用溶剂漂洗后套用，滤液直接加水洗，分层，再用碳酸氢钠水溶液洗到中性后，分层，有机层回收溶剂后精馏，得纯的产品2-溴乙基甲基醚。6. The preparation method according to claim 1, characterized in that after the decomposition reaction is finished, add water first to convert the boric acid derivatives produced into boric acid, the boric acid recovered by filtration is rinsed with a solvent and applied mechanically, the filtrate is directly washed with water, layered, and then After washing with sodium bicarbonate aqueous solution to neutrality, the layers were separated, and the organic layer was rectified after recovering the solvent to obtain the pure product 2-bromoethyl methyl ether.
CN2009101530112A 2009-09-25 2009-09-25 Preparation method of 2-bromoethyl methyl ether Active CN101671238B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN2009101530112A CN101671238B (en) 2009-09-25 2009-09-25 Preparation method of 2-bromoethyl methyl ether

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN2009101530112A CN101671238B (en) 2009-09-25 2009-09-25 Preparation method of 2-bromoethyl methyl ether

Publications (2)

Publication Number Publication Date
CN101671238A CN101671238A (en) 2010-03-17
CN101671238B true CN101671238B (en) 2012-07-04

Family

ID=42018689

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2009101530112A Active CN101671238B (en) 2009-09-25 2009-09-25 Preparation method of 2-bromoethyl methyl ether

Country Status (1)

Country Link
CN (1) CN101671238B (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006064897A1 (en) * 2004-12-16 2006-06-22 Manac Inc. Process for producing 2-alkoxyethyl bromide

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006064897A1 (en) * 2004-12-16 2006-06-22 Manac Inc. Process for producing 2-alkoxyethyl bromide

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Development》.2007,第11卷468-469. *
Varaprasad Dasari.A Facile Process for the Preparation of 2-Bromoethyl Methyl Ether.《Organic Process Research & Development》.2007,第11卷468-469.
Varaprasad Dasari.A Facile Process for the Preparation of 2-Bromoethyl Methyl Ether.《Organic Process Research &amp *

Also Published As

Publication number Publication date
CN101671238A (en) 2010-03-17

Similar Documents

Publication Publication Date Title
CN101891649B (en) Novel 3-cyano methyl benzoate preparing method
CN104119367A (en) Preparation method of aryl boric acid
CN111320535B (en) Preparation method of 3- (benzyloxy) -1-cyclobutanone
CN106632014B (en) A kind of preparation method of 2-amino-5-chloropyridine
CN101704723B (en) Preparation method of hydroxymethyl substitutent o-alkyl biphenyl and intermediate thereof
CN105732298B (en) A kind of synthetic method of the fluorenes of 1 bromine, 9,9 ' spiral shell two
CN101671238B (en) Preparation method of 2-bromoethyl methyl ether
CN101851225B (en) Method for synthesizing fludioxonil intermediate 4-aldehyde-2,2-difluorobenzodioxole
CN112979612B (en) A kind of method for preparing 2-iodo heterocyclic aryl ether at room temperature
CN113234099B (en) Photochemical synthesis method of alkyl borate compound
CN102675148B (en) The preparation method of p-hydroxybenzonitrile
CN101781205B (en) Method for synthesizing substitutional crylic acid phenyl ester
CN105622334B (en) A kind of synthetic method of the fluorenes of 3 bromine, 9,9 ' spiral shell two
CN101891761B (en) Method for catalytically synthesizing triethyl phosphate by phase transfer
CN101665415B (en) Preparation method of 2-(2-chloroethyl) ethanol
CN107602337B (en) Preparation method of 1,4-dicyano-2-butene
CN116003216B (en) A kind of preparation method of ibuprofen
CN105294416B (en) A kind of 1,5 Dicarbonyl derivatives and preparation method thereof
CN103058884A (en) Method for synthesizing 1-hydroxymethyl cyclopropyl acetonitrile
CN116217352B (en) A method for preparing cannabinoids and cannabinoids
CN102746358B (en) A kind of technique of synthesizing pregnant steroid 21 bromides
WO2022174468A1 (en) Method for preparing 2-iodoheterocyclic aryl ether at room temperature
CN102558196A (en) Method for preparing (3,4)-1,4-dioxoethylidene thiophene-2'-methanol
WO2008059960A1 (en) Method for producing quarter-pyridine derivative and intermediate of quarter-pyridine derivative
WO2024087157A1 (en) Method for synthesizing key intermediate of tegoprazan

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CP01 Change in the name or title of a patent holder

Address after: 225654, Jiangsu City, Gaoyou province Guo Town Pier Village

Patentee after: Yangzhou Prince Pharmaceutical Technology Co.,Ltd.

Patentee after: SHAOXING University

Address before: 225654, Jiangsu City, Gaoyou province Guo Town Pier Village

Patentee before: YANGZHOU PRINCECHEM Co.,Ltd.

Patentee before: SHAOXING University

CP01 Change in the name or title of a patent holder