CN108069901A - A kind of Rebamipide new technique for synthesizing - Google Patents
A kind of Rebamipide new technique for synthesizing Download PDFInfo
- Publication number
- CN108069901A CN108069901A CN201611008664.8A CN201611008664A CN108069901A CN 108069901 A CN108069901 A CN 108069901A CN 201611008664 A CN201611008664 A CN 201611008664A CN 108069901 A CN108069901 A CN 108069901A
- Authority
- CN
- China
- Prior art keywords
- compound
- sodium
- acid
- carbonate
- reaction
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of Rebamipide new technique for synthesizing.Then the present invention obtains chlorimide intermediate using glycine methyl ester as starting material by amidation, chloro, chlorimide intermediate is reacted with bromomethyl quinolone, then hydrolyzes to obtain Rebamipide.The present invention has many advantages, such as that starting material is cheap and easy to get, reaction yield is high, is easy to industrialization.
Description
Technical field
The present invention relates to medication chemistry technology, more specifically to a kind of new technique for synthesizing of Rebamipide.
Background technology
Rebamipide（Rebamipide）, be a kind of chemical formula such as（1）Shown carbostyril compound, chemical name
For：2- (4- chIorobenzoyIaminos) -3- (2 (1H)-quinolone -4- bases) propionic acid, Yuan Yan producers are the big tomb pharmacy strain formula meeting of Japan
Society.Rebamipide is the gastric mucosa protectant of active a new generation, can improve the histology healing quality of gastric ulcer, and reduce and burst
Ulcer recurs, and treating the gastric mucosa damage caused by the factors such as non-steroid anti-inflammatory drug (NSAIDs), alcohol has good action, right
Still there is good efficacy in the gastric mucosal lesion for failing to eradicate H.pylori infection, and be uniquely have both increase PG synthesis with it is clear
It removes and inhibits the gastric mucosa protectant of Free Radical, there is higher clinical value.
The preparation method of Rebamipide, multiple patents all have been reported that usually there are following three kinds of synthetic methods：Method one, day
Synthetic route disclosed in this patent JP2008-143794A, diacetanilide generate bromomethyl quinolone through bromo, closed loop（2）, 2
Generation quinolone diethyl malonate is reacted under the action of alkali with acetamino diethyl malonate（4）, take off under 4 acid conditions
Deacetylate and carboxyl obtain carbostyril amino acid compound（5）, 5 generate Rebamipide with parachlorobenzoyl chloride reaction（1）.Its
Reaction process is shown below：
。
Method two, bromomethyl quinolone（2）With p-chlorobenzamido diethyl malonate（7）It reacts in alkaline conditions
Compound 8 is obtained, obtains Rebamipide through deacetylation, decarboxylation, reaction process is shown below：
。
Method three, Morita et al. is in proposition in 1991, bromomethyl quinolone（2）Chemical combination is generated under phosphorus oxychloride effect
Object 9, compound 9 are obtained by the reaction compound 11 with compound 10, compound 12, hydrolyzed under acidic conditions generationization are obtained through open loop
Object 5 is closed, reacts generation Rebamipide with compound 6.Its reaction process is shown below：
。
Above-mentioned three kinds of preparation methods, starting material is expensive, and complex production process is of high cost, is not easy to industrialize, and produces work
Skill does not possess market competition advantage, and the present invention is developed a kind of raw material and be easy to get, be at low cost, is capable of being industrialized using cheap raw material
Rebamipide new preparation process.
The content of the invention
It is not easy to obtain present invention mainly solves Rebamipide raw material, the problems such as process conditions are harsh, production cost is high, purpose
It is to provide a kind of new preparation process of Rebamipide.
Present invention employs following technical proposals：
The present invention provides a kind of new technique for synthesizing of Rebamipide, process route is as follows：
It is as follows including step：
1）Using glycine methyl ester as starting material, amidation process obtains compound 14；
2）Compound 14 occurs chlorination and obtains compound 15；
3）Compound 15 occurs substitution reaction with compound 2 and obtains compound 16；
4）Compound 16 is through hydrolyzing to obtain compound 1.
In step 1）In, with parachlorobenzoyl chloride amidation process generation chemical combination occurs in alkaline conditions for glycine methyl ester
Object 14.The one kind or their mixing of reaction dissolvent in dichloromethane, chloroform, dichloroethanes, ether, isopropyl ether, toluene
Object, preferred solvent are dichloromethane；One kind in triethylamine, sodium hydroxide, sodium carbonate, sodium acid carbonate, potassium carbonate of alkali or
It is a variety of, preferred triethylamine；Reaction temperature is selected from 0~30 DEG C, preferably 5~10 DEG C.Selection process data statistics is as follows：
| Number | Reaction dissolvent | Alkali | Yield |
| 1-1 | Dichloromethane | Triethylamine | 95% |
| 1-3 | Ether | Sodium acid carbonate | 91% |
| 1-3 | Tetrahydrofuran | Sodium carbonate | 87% |
In step 2）In, compound 14 reacts with halogenating agent and generates compound 15.Reaction dissolvent is selected from dichloromethane, chlorine
Imitative, one kind in dichloroethanes, ether, isopropyl ether, tetrahydrofuran, toluene or their mixture, preferably toluene；Halogenating agent
One kind in phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, preferably phosphorus pentachloride；Reaction temperature be selected from 20~
120 DEG C, preferably 80~110 DEG C.Selection process data statistics is as follows：
| Number | Reaction dissolvent | Halogenating agent | Yield |
| 2-1 | Dichloromethane | Five phosphorous oxides | 86% |
| 2-2 | Toluene | Five phosphorous oxides | 91% |
| 2-3 | Toluene | Phosphorus trioxide | 84% |
| 2-4 | Isopropyl ether | Phosphorus trioxide | 66% |
| 2-5 | Chloroform | Phosphorus trioxide | 77% |
In step 3）In, substitution reaction generation compound 16 occurs in alkaline conditions with compound 2 for compound 15.Reaction dissolvent
In water, methanol, ethyl alcohol, acetone, acetonitrile, tetrahydrofuran, dioxane, ether, isopropyl ether, toluene, dichloromethane, chloroform
One kind or their mixture, preferred solvent be methanol；Alkali is selected from triethylamine, sodium hydroxide, sodium carbonate, sodium acid carbonate, carbon
Sour potassium, one in sodium methoxide, sodium ethoxide, sodium tert-butoxide, n-BuLi, lithium diisopropylamine, hexamethyldisilazide lithium
Kind is a variety of, preferably sodium hydroxide.Selection process data statistics is as follows：
| Number | Solvent | Alkali | Yield |
| 3-1 | Toluene | Triethylamine | 80% |
| 3-2 | Methanol | Sodium hydroxide | 88% |
| 3-3 | Ethyl alcohol | Sodium ethoxide | 84% |
| 3-4 | Tetrahydrofuran | N-BuLi | 56% |
| 3-5 | Dichloromethane | Triethylamine | 75% |
In step 4）In, compound 16 hydrolyzes generation compound 1 under basic or acidic conditions.Solvent is selected from water, methanol, second
One kind or their mixture, preferred solvent in alcohol, normal propyl alcohol, isopropanol, acetone, tetrahydrofuran, dioxane, acetonitrile are
The mixture of first alcohol and water；Alkali is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, sodium acid carbonate, potassium carbonate, and one in triethylamine
Kind is a variety of, preferably sodium hydroxide；Acid is one or more selected from hydrochloric acid, dilute sulfuric acid, phosphoric acid, formic acid, acetic acid, pyrovinic acid, excellent
Select hydrochloric acid.Selection process data statistics is as follows：
| Number | Solvent | Acid or alkali | Yield |
| 4-1 | Methanol | Sodium hydroxide | 92% |
| 4-2 | 95% ethyl alcohol | Sodium hydroxide | 93% |
| 4-3 | Acetone | Sodium carbonate | 86% |
| 4-4 | 80% ethyl alcohol | Hydrochloric acid | 75% |
Compared to the prior art, the present invention has following advantageous effects：1. cost substantially reduces, using glycine methyl ester as rise
Beginning raw material, technique is simpler, and the acetylamino malonic ester used in other process routes needs multistep to synthesize；2. technique
Mild condition avoids decarboxylation step from reacting halfway when leading to the problem of bubble, is easy to industrialize.
Specific embodiment
Technical scheme is further described below by embodiment, for those of ordinary skill in the art
Speech, the following example do not form the limitation to protection scope of the present invention.
Embodiment 1
To chlorobenzoyl glycine methyl ester（Compound 14）：
12.5 g of glycine methyl ester hydrochloride (100 mmol), dichloromethane 125ml, triethylamine are added in reaction bulb
30.3g is cooled to 0~5 DEG C, and parachlorobenzoyl chloride 18.4g is added dropwise（105mmol）, heat up 25 DEG C of reaction 4 h, TLC prisons after adding
Control reactant is fully converted to product（Solvent：Dichloromethane）.Reaction finishes, and adds in water 30mL stirrings, separates organic layer, water
Layer adds methylene chloride, and 30ml extractions are secondary, and merging organic layer is washed to neutrality, and the drying of 20g anhydrous sodium sulfates filters drier,
It is concentrated under reduced pressure into without solid 21.5g until slipping out object, is obtained, yield 95% is directly used in the next step without refined.ESI-MS
(m/z ) : 228 [M+1]+。
The synthesis of chlorimide intermediate（Compound 15）：
Chlorobenzoyl glycine methyl ester 21.5g (94 mmol) will be dissolved in 120ml dichloroethanes, and add in phosphorus pentachloride 39.5g
（188mmol）, 84 DEG C or so are warming up to, is stirred to react 2h, the reaction was complete for TLC monitoring（Solvent：Ethyl acetate:Dichloromethane=
1:3）, decompression is spin-dried for solvent and obtains grease 20g, yield 86%.ESI-MS (m/z ) :247 [M+1]+。
The synthesis of substituent（Compound 16）：
15 20g of compound (81 mmol), toluene 100mL, 2 21.2g of compound are added in reaction bulb（85.8mmol）
Triethylamine 12.3g (121 mmol), finishes, and is warming up to 70~80 DEG C of reaction 5 h, TLC monitoring reactants and is fully converted to produce
Object（Solvent：Ethyl acetate：Dichloromethane=1:1）.Room temperature is cooled to, water 30ml*3 is added to be washed till neutrality, anhydrous sodium sulphate drying is taken out
It filters, be spin-dried for obtaining white solid, 50 DEG C of vacuum dryings 3 obtain 29.5g, yield 90% when small.ESI-MS (m/z ) : 404[M+1]+。
Rebamipide and synthesis（Compound 1）：
16 29.5g of compound (73.2 mmol), methanol 100 mL, 10% sodium hydroxide 80ml heating are added in reaction bulb
To 60~65 DEG C be stirred to react 3 it is small when, TLC monitoring reactant be fully converted to product（Solvent：Methanol：Dichloromethane=1:
3）.Reaction finishes, and is cooled to 10 DEG C or so, and 5% hydrochloric acid adjusts PH and refers to 4 or so, and white solid, filtering, 50 DEG C of vacuum dryings are precipitated
3 obtain solid 24.9g, yield 92% when small.ESI-MS (m/z ) : 371[M+1]+。
Embodiment 2
To chlorobenzoyl glycine methyl ester（Compound 14）：
12.5 g of glycine methyl ester hydrochloride (100 mmol), ether 125ml, sodium acid carbonate 25.2g are added in reaction bulb
（300mmol）, 0~5 DEG C is cooled to, parachlorobenzoyl chloride 18.4g is added dropwise（105mmol）, heat up 25 DEG C of 4 h of reaction after adding,
TLC monitoring reactants are fully converted to product（Solvent：Dichloromethane）.Reaction finishes, and adds in water 30mL stirrings, separates organic
Layer, water layer adds methylene chloride, and 30ml extractions are secondary, and merging organic layer is washed to neutrality, and anhydrous sodium sulfate drying filters drying
Agent is concentrated under reduced pressure into without solid 20.6g until slipping out object, is obtained, and yield 91% is directly used in the next step without refined.ESI-MS
(m/z ) : 228 [M+1]+。
The synthesis of chlorimide intermediate（Compound 15）：
Chlorobenzoyl glycine methyl ester 20.6g (91 mmol) will be dissolved in 120ml toluene, and add in phosphorus pentachloride 37.9g
（182mmol）, 80 DEG C or so are warming up to, is stirred to react 3h, the reaction was complete for TLC monitoring（Solvent：Ethyl acetate:Dichloromethane=
1:3）, decompression is spin-dried for solvent and obtains grease 20.3g, yield 91%.ESI-MS (m/z ) :247 [M+1]+。
The synthesis of substituent（Compound 16）：
15 20.3g of compound (82.5 mmol), methanol 100mL, 2 21.2g of compound are added in reaction bulb
（85.8mmol）, sodium hydroxide 5g (125 mmol) finishes, and is warming up to 60 DEG C of reaction 5 h, TLC monitoring reactants and turns completely
Turn to product（Solvent：Ethyl acetate：Dichloromethane=1:1）.Solvent is spin-dried for after completion of the reaction, and add methylene chloride 100ml, adds
Water 30ml*3 is washed till neutrality, and anhydrous sodium sulphate drying filters, is spin-dried for obtaining white solid, 50 DEG C of vacuum dryings 3 obtain 29.2g, yield when small
88%。ESI-MS (m/z ) : 404[M+1]+。
Rebamipide and synthesis（Compound 1）：
16 29.2g of compound (72.4 mmol), 95% ethyl alcohol, 100 mL, 10% sodium hydroxide 80ml liters are added in reaction bulb
Temperature to 60~65 DEG C be stirred to react 3 it is small when, TLC monitoring reactant be fully converted to product（Solvent：Methanol：Dichloromethane=1:
3）.Reaction finishes, and is cooled to 10 DEG C or so, and 5% hydrochloric acid adjusts PH and refers to 4 or so, and white solid, filtering, 50 DEG C of vacuum dryings are precipitated
3 obtain solid 24.9g, yield 93% when small.ESI-MS (m/z ) : 371[M+1]+。
Claims (5)
1. a kind of new technique for synthesizing of Rebamipide, process route are as follows：
It is characterized in that the technique comprises the following steps：
1）Using glycine methyl ester as starting material, compound 14 is reacted to obtain with parachlorobenzoyl chloride；
2）Compound 14 occurs chlorination and obtains compound 15；
3）Compound 15 occurs substitution reaction with compound 2 and obtains compound 16；
4）Compound 16 is through hydrolyzing to obtain compound 1.
2. preparation method described in accordance with the claim 1, it is characterised in that：In step 1）In, glycine methyl ester with to chlorobenzene first
Amidation process generation compound 14 occurs in alkaline conditions for acyl chlorides；Reaction dissolvent is selected from dichloromethane, chloroform, two chloroethenes
One kind or their mixture in alkane, ether, isopropyl ether, toluene；Alkali is selected from triethylamine, sodium hydroxide, sodium carbonate, bicarbonate
One or more in sodium, potassium carbonate.
3. preparation method described in accordance with the claim 1, it is characterised in that：In step 2）In, compound 14 is sent out with halogenating agent
Raw reaction generation compound 15；Reaction dissolvent is selected from dichloromethane, chloroform, dichloroethanes, ether, isopropyl ether, tetrahydrofuran, first
One kind or their mixture in benzene；Halogenating agent is in phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride
It is a kind of.
4. preparation method described in accordance with the claim 1, it is characterised in that：In step 3）In, compound 15 is in alkaline conditions
Substitution reaction generation compound 16 occurs with compound 2；Reaction dissolvent is selected from water, methanol, ethyl alcohol, acetone, acetonitrile, tetrahydrochysene furan
It mutters, one kind in dioxane, ether, isopropyl ether, toluene, dichloromethane, chloroform or their mixture；Alkali is selected from three second
Amine, sodium hydroxide, sodium carbonate, sodium acid carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, n-BuLi, diisopropyl ammonia
One or more in base lithium, hexamethyldisilazide lithium.
5. preparation method described in accordance with the claim 1, it is characterised in that：In step 4）In, compound 16 is in alkalescence or acid
Under the conditions of hydrolysis generation compound 1；Solvent is selected from water, methanol, ethyl alcohol, normal propyl alcohol, isopropanol, acetone, tetrahydrofuran, dioxy six
One kind or their mixture in ring, acetonitrile；Alkali is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, sodium acid carbonate, potassium carbonate,
One or more in triethylamine；Acid is one or more selected from hydrochloric acid, dilute sulfuric acid, phosphoric acid, formic acid, acetic acid, pyrovinic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611008664.8A CN108069901B (en) | 2016-11-16 | 2016-11-16 | Novel rebamipide synthesis process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611008664.8A CN108069901B (en) | 2016-11-16 | 2016-11-16 | Novel rebamipide synthesis process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108069901A true CN108069901A (en) | 2018-05-25 |
| CN108069901B CN108069901B (en) | 2020-12-11 |
Family
ID=62163131
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611008664.8A Active CN108069901B (en) | 2016-11-16 | 2016-11-16 | Novel rebamipide synthesis process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108069901B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107674023A (en) * | 2017-11-16 | 2018-02-09 | 重庆理工大学 | A kind of synthetic method of Rebamipide |
| CN115028579A (en) * | 2022-06-21 | 2022-09-09 | 福建海西新药创制有限公司 | Synthetic method of rebamipide bulk drug |
| CN115524417A (en) * | 2022-09-19 | 2022-12-27 | 杭州沐源生物医药科技有限公司 | Analysis method of related substances and isomers of rebamipide tablets |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002066436A1 (en) * | 2001-02-20 | 2002-08-29 | Kyung Dong Pharm., Co., Ltd | Process for preparing 2-(4-chlorobenzolamino) -3-[2(1h) -quinolinon-4-yl]proprionic acid |
| JP2008143794A (en) * | 2006-12-06 | 2008-06-26 | Otsuka Pharmaceut Co Ltd | Method for producing carbostyryl compound for medicine |
-
2016
- 2016-11-16 CN CN201611008664.8A patent/CN108069901B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002066436A1 (en) * | 2001-02-20 | 2002-08-29 | Kyung Dong Pharm., Co., Ltd | Process for preparing 2-(4-chlorobenzolamino) -3-[2(1h) -quinolinon-4-yl]proprionic acid |
| US20030087930A1 (en) * | 2001-02-20 | 2003-05-08 | Lee Byoung-Suk | Process for preparing 2-(4-chlorobenzolamino)-3[ (1h)-quinolinon-4-yl] propionic acid |
| JP2008143794A (en) * | 2006-12-06 | 2008-06-26 | Otsuka Pharmaceut Co Ltd | Method for producing carbostyryl compound for medicine |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107674023A (en) * | 2017-11-16 | 2018-02-09 | 重庆理工大学 | A kind of synthetic method of Rebamipide |
| CN115028579A (en) * | 2022-06-21 | 2022-09-09 | 福建海西新药创制有限公司 | Synthetic method of rebamipide bulk drug |
| CN115028579B (en) * | 2022-06-21 | 2023-07-18 | 福建海西新药创制股份有限公司 | Synthesis method of rebamipide bulk drug |
| CN115524417A (en) * | 2022-09-19 | 2022-12-27 | 杭州沐源生物医药科技有限公司 | Analysis method of related substances and isomers of rebamipide tablets |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108069901B (en) | 2020-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108069901A (en) | A kind of Rebamipide new technique for synthesizing | |
| CN108440409B (en) | Green and efficient preparation method of rebamipide | |
| CN102164897A (en) | Method for preparing montelukast sodium salts | |
| CN101952245A (en) | Carbonic and sulphuric acid salts of 3-(2,2,2-trimethylhydrazinium)propionate esters and their use for 3-(2,2,2-trimethylhydrazinium)propionate dihydrate preparation | |
| KR20040099279A (en) | Method for preparing benzisoxazole methane sulfonyl chloride and its amidation to form zonisamide | |
| CN107674023A (en) | A kind of synthetic method of Rebamipide | |
| KR100520184B1 (en) | Improved method for the preparation of rebamipide | |
| JP2010043053A (en) | Process for producing high purity rebamipide | |
| CN108610290A (en) | A kind of preparation method of fluorine azoles bacterium acyl azanol | |
| CN105777581A (en) | Cis-1-cyano-4-methoxycyclohexyl-2-(2, 5-dimethylphenyl)acetamide, preparation method and application thereof | |
| CN104876911A (en) | Simple method for synthesizing delafloxacin | |
| KR101469015B1 (en) | Method for the preparation of Montelukast and intermediates used therein | |
| JP2003201281A (en) | Method for producing 4-(2-methyl-1-imidazolyl)-2,2- diphenylbutane amide | |
| CN110938036A (en) | Preparation method of 4-iodine-1H-imidazole | |
| CN108129396A (en) | A kind of synthesis 1-（3- chloropropyls）The method of 2-ketone benzimidaozole | |
| CN106866560A (en) | A kind of synthetic method of Lesinurad | |
| CN117567404A (en) | Preparation method of (Z) -alpha- (methoxyimino) furan-2-acetic acid | |
| CN103695522B (en) | A kind of preparation method of Cefditoren pivoxil Cephalosporins intermediate | |
| KR100503267B1 (en) | Method for the preparation of 2-acetyloxy-4-trifluoromethyl benzoic acid | |
| CN101759556B (en) | Synthesis method of ketoprofen | |
| JP3573249B2 (en) | 2,3,4-trifluoro-5-iodobenzoic acid, esters thereof and process for producing the same | |
| WO2003042193A1 (en) | Process for preparing 5-methylisoxazole-4-carboxylic-(4'-trifluoromethyl)-anilide | |
| JP2009196951A (en) | Method for producing alkyl hydrosulfide compound or derivative thereof | |
| CN101591236B (en) | Method for synthesizing ketoprofen through channelization | |
| CN111004120A (en) | Preparation method of di-p-methoxybenzoyl tartaric acid |
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 |