CN107721901A - A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid - Google Patents
A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid Download PDFInfo
- Publication number
- CN107721901A CN107721901A CN201711110381.9A CN201711110381A CN107721901A CN 107721901 A CN107721901 A CN 107721901A CN 201711110381 A CN201711110381 A CN 201711110381A CN 107721901 A CN107721901 A CN 107721901A
- Authority
- CN
- China
- Prior art keywords
- phenyl
- amido
- acetic acid
- reaction
- preparation
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
Abstract
The present invention relates to a kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid, belong to the production technical field of NSAIDs;The present invention is first with the synthesis ketone of 1 (2,3,5,6 tetrafluoro phenyl) indoles 2 under lewis acid, dichloro-benzenes, 2 chlorine N (4 ethylphenyl) N (2,3,5,6 tetrafluoro phenyl) acetamide certain condition;Then using the ketone of 1 (2,3,5,6 tetrafluoro phenyl) indoles 2, alkali and water as raw material certain condition under synthesize 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid;Product purity prepared by the present invention reaches more than 98%, and yield is up to 90.22%;The preparation method of the present invention, it is simple to operate, cumbersome subtractive process is avoided, power consumption is low, green, is expected to be applied in industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid, belong to non-steroidal
The production technical field of anti-inflammatory agent.
Background technology
Rofecoxib (Robenacoxib), chemical name:2- [2- (2,3,5,6- phenyl tetrafluorides amido) -5- ethylphenyls]
Acetic acid, it is that one kind is used for pain of alleviation, is mainly used in the nonsteroidal anti-inflammatory drug of arthritis treatment, with other NSAIDs
(such as brufen and naproxen) is compared, and rofecoxib has less gastrointestinal side effect, have lower gastroenteritic ulcer and
The risk of bleeding, and the NSAIDs for having relatively low such adverse reaction rate being uniquely proved to.
2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid is similar with rofecoxib structure, is synthesizing
It is easy to produce impurity 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid during Robenacoxib, and passes through
The process for purification such as in general recrystallization are difficult that it is removed or controlled within the scope of very little from Robenacoxib, are ground
Studying carefully the synthetic method of 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid turns into the pass of control Robenacoxib quality controls
Key, there is directive significance for the building-up process and quality control for studying rofecoxib, and carried for the quality research of rofecoxib
The thinking of Control of Impurities is supplied.
The content of the invention
The invention provides a kind of preparation method of 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid.
The reaction equation that the present invention prepares 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid is as follows:
Wherein, compound (1) is the chloro- N- of 2- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoro phenyl) acetamide, compound
(2) it is 1- (2,3,5,6- tetrafluoro phenyl) indol-2-one, compound (3) is 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl]
Acetic acid.
Specifically, comprise the following steps in embodiments of the invention:
(1) 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one is synthesized:
Under nitrogen protection, a certain amount of lewis acid and solvent are added in reaction bulb, after a period of time is stirred at room temperature, slowly
It is slow to add 2- chloro- N- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoro phenyl) acetamide, certain temperature, reaction a period of time;
After reaction solution is down to certain temperature, reaction solution is poured into progress ice solution in mixture of ice and water, filtering, obtained solid product is used
After water washing, then washed with n-hexane, dry, obtain 1- (2,3,5,6- tetrafluoro phenyl) indol-2-one;
(2) 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid is synthesized:
A certain amount of solvent and alkali are added in reaction bulb, add a certain amount of 1- (2,3,5,6- tetrafluoro phenyl) indoles-
2- ketone, certain temperature is risen to, reaction a period of time, after reaction solution is down into certain temperature, reaction solution pH to one is adjusted with hydrochloric acid
Definite value, filtering, obtained solid product are washed with water, and dry, obtain 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid.
Wherein in step (1), the solvent is dichloro-benzenes;The lewis acid is boron trifluoride, alchlor, tri-chlorination
Iron or antimony pentafluoride;The lewis acid rubs with the chloro- N- of 2- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoros phenyl) acetamide
You are than being 1~3:1;The time being stirred at room temperature is 30min;Reaction temperature is 140~160 DEG C, and the reaction time is 5~10h;Reaction
The temperature that liquid is down to is less than 50 DEG C;
Wherein in step (2), the solvent is water or the mixed solution of water and alcohol;The mixed solution reclaimed water of the water and alcohol
Mass ratio with alcohol is 600:60~200;The alcohol is methanol or ethanol;The alkali is sodium hydroxide or potassium hydroxide;Alkali with
The mol ratio of 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one is 1~3:1, reaction temperature is 80~100 DEG C, the reaction time 5
~10h;The temperature that reaction solution is down to is less than 60 DEG C;PH value after reaction solution regulation is 3~4.
Compared with prior art, advantage of the invention is that:
The invention provides a kind of preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid, Fu make use of
The back reaction of gram alkylation reaction, ethyl is set to depart from phenyl ring and obtain 2- [2- (2,3,5,6- phenyl tetrafluorides simultaneously during cyclization
Amido) phenyl] acetic acid.The purity of 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid that the present invention synthesizes and yield compared with
Height, the purity of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid reach more than 98%, and yield is up to 90.22%.This hair
Bright preparation method is simple, avoids the cumbersome preparation process of prior art, and power consumption is low, green, while is research sieve sheet
Examine the synthesis of former times and the generation process of impurity provides foundation.
Brief description of the drawings
Fig. 1 is the nucleus magnetic hydrogen spectrum of 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid that the present invention is prepared.
Embodiment
With reference to specific embodiment, the present invention will be further described.
Embodiment 1:
(1) 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one is synthesized:
Dichloro-benzenes 230ml, alchlor 0.4mol are added into tetra- mouthfuls of reaction bulbs of 500ml under nitrogen protection, is stirred at room temperature
30min, 0.4mol 2- chloro- N- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoro phenyl) acetamide is added, then heats to 150
DEG C, insulation reaction 10h, reaction terminates;Reaction solution is cooled to 50 DEG C, and reaction solution is poured into progress ice solution, ice in 600g frozen water
After solution terminates, reaction solution is filtered;Obtained solid product is washed with after substantial amounts of water washing, then with appropriate n-hexane
Wash, dry solid product, obtain 100g 1- (2,3,5,6- tetrafluoro phenyl) indol-2-one, yield 87.80%.
(2) 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid is synthesized:
Water 600g, sodium hydroxide 0.6mol are added in tetra- mouthfuls of reaction bulbs of 1L, adds 0.3mol 1- (2,3,5,6- tetrafluoros
Phenyl) indol-2-one, 100 DEG C are warming up to, insulation reaction 8h;Then the temperature of reaction solution is down to 60 DEG C, adjusted with hydrochloric acid anti-
The pH to 3 of liquid is answered, filters, obtained solid product is washed with water, drying is taken out and obtains 96g 2- [2- (2,3,5,6- tetrafluoros
Anilino-) phenyl] acetic acid, yield 90.22%.
Embodiment 2:
(1) 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one is synthesized:
Dichloro-benzenes 230ml, ferric trichloride 0.8mol are added into tetra- mouthfuls of reaction bulbs of 500ml under nitrogen protection, is stirred at room temperature
30min, 0.4mol 2- chloro- N- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoro phenyl) acetamide is added, then heats to 160
DEG C, insulation reaction 8h, reaction terminates;Reaction solution is cooled to 40 DEG C and reaction solution is poured into progress ice solution, ice solution in a large amount of frozen water
Terminate filtering, solid massive laundering, finally washed, be filtered dry with n-hexane, solid is dried to obtain 93g 1- (2,3,5,6- tetrafluoros
Phenyl) indol-2-one, yield 81.65%.
(2) 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid is synthesized:
Water 600g, potassium hydroxide 0.6mol are added in tetra- mouthfuls of reaction bulbs of 1L, adds 0.3mol 1- (2,3,5,6- tetrafluoros
Phenyl) indol-2-one, 80 DEG C of insulation reaction 10h are warming up to, reaction solution is then cooled to 50 DEG C, with salt acid for adjusting pH to 3,
Filtering, obtained solid product are washed with water, and 80.44g 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] second is dried to obtain in taking-up
Acid, yield 84%.
Embodiment 3:
(1) 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one is synthesized:
Dichloro-benzenes 230ml, boron chloride 0.7mol are added into tetra- mouthfuls of reaction bulbs of 500ml under nitrogen protection, is stirred at room temperature
30min, 0.4mol 2- chloro- N- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoro phenyl) acetamide is added, then heats to 155
DEG C, insulation reaction 5h, reaction terminates;Reaction solution is cooled to 30 DEG C, and reaction solution is poured into progress ice solution, ice solution in a large amount of frozen water
Terminate filtering, obtained solid product is washed with massive laundering, finally washed with n-hexane, is filtered dry, and solid is dried to obtain 91g 1-
(2,3,5,6- tetrafluoro phenyl) indol-2-one, yield 79.9%.
(2) 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid is synthesized:
Water 600g, methanol 60g, potassium hydroxide 0.3mol are added in tetra- mouthfuls of reaction bulbs of 1L, add 0.3mol 1- (2,3,
5,6- tetrafluoro phenyl) indol-2-one, 90 DEG C of insulation reaction 6h are warming up to, methanol is evaporated off, then reaction solution is cooled to 50 DEG C, uses
To 4, filtering, obtained solid product is washed with water salt acid for adjusting pH, takes out drying, obtains 90.85g 2- [2- (2,3,5,6-
Phenyl tetrafluoride amido) phenyl] acetic acid, yield 94.87%.
Embodiment 4:
(1) 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one is synthesized:
Dichloro-benzenes 230ml, antimony pentafluoride 1.2mol are added into tetra- mouthfuls of reaction bulbs of 500ml under nitrogen protection, is stirred at room temperature
30min, 0.4mol 2- chloro- N- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoro phenyl) acetamide is added, then heats to 140
DEG C, insulation reaction 6h, reaction terminates;Reaction solution is cooled to 50 DEG C, and reaction solution is poured into progress ice solution, ice solution in a large amount of frozen water
Terminate filtering, obtained solid product is washed with massive laundering, finally washed with n-hexane, is filtered dry, and solid is dried, and obtains 96.46g
1- (2,3,5,6- tetrafluoro phenyl) indol-2-one, yield 84.71%.
(2) 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid is synthesized:
Water 600g, ethanol 200g, sodium hydroxide 0.9mol are added in tetra- mouthfuls of reaction bulbs of 1L, add 0.3mol 1- (2,3,
5,6- tetrafluoro phenyl) indol-2-one, 90 DEG C of insulation reaction 5h are warming up to, ethanol is evaporated off, reaction solution is then cooled to 50 DEG C,
With salt acid for adjusting pH to 4, filtering, obtained solid product is washed with water, and takes out drying, obtain 91.65g 2- [2- (2,3,5,
6- phenyl tetrafluorides amido) phenyl] acetic acid, yield 95.71%.
Fig. 1 is the nucleus magnetic hydrogen spectrum of 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid that the present invention is prepared.By
Fig. 1 is it was determined that (d6-DMSO):3.750 (s, 2H) are attributed to methylene hydrogen, and 6.8~7.5 (6H) are attributed on two phenyl ring
Hydrogen, 7.750 (s, H) are attributed to amino hydrogen, and 12.509 (s, H) are attributed to carboxylic hydroxy group's hydrogen.Analyzed by above nucleus magnetic hydrogen spectrum, can
To show that the material that the present invention is prepared is 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid.
Claims (10)
1. a kind of preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid, it is characterised in that including following step
Suddenly:
(1)Synthesize 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one:
Under nitrogen protection, a certain amount of lewis acid and solvent are added in reaction bulb, after a period of time is stirred at room temperature, is slowly added
Enter the chloro- N- of 2- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoro phenyl) acetamide, certain temperature, reaction a period of time;Reaction
After liquid is down to certain temperature, reaction solution is poured into progress ice solution in mixture of ice and water, filtering, obtained solid product is washed with water
After washing, then washed with n-hexane, dry, obtain 1- (2,3,5,6- tetrafluoro phenyl) indol-2-one;
(2)Synthesize 2- [2- (2,3,5,6- phenyl tetrafluorides amido) phenyl] acetic acid:
A certain amount of solvent and alkali are added in reaction bulb, adds a certain amount of 1- (2,3,5,6- tetrafluoro phenyl) indol-2-one,
Rise to certain temperature, reaction a period of time, after reaction solution is down into certain temperature, reaction solution pH adjusted to certain value with hydrochloric acid,
Filtering, obtained solid product are washed with water, and dry, obtain 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid.
2. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(1)In, the solvent is dichloro-benzenes;The lewis acid is boron trifluoride, alchlor, ferric trichloride or five
Antimony fluoride.
3. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(1)Described in lewis acid and the chloro- N- of 2- (4- ethylphenyls)-N- (2,3,5,6- tetrafluoros phenyl) acetamide
Mol ratio is 1 ~ 3:1.
4. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(1)Described in time for being stirred at room temperature be 30min.
5. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(1)Described in reaction temperature be 140~160 DEG C, the reaction time is 5~10 h.
6. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(1)Described in the temperature be down to of reaction solution be less than 50 DEG C.
7. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(2)In, the solvent is water or the mixed solution of water and alcohol;The mixed solution reclaimed water of the water and alcohol and alcohol
Mass ratio is 600:60~200;The alcohol is methanol or ethanol;The alkali is sodium hydroxide or potassium hydroxide, and described alcohol is first
Alcohol or ethanol.
8. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(2)Described in the mol ratio of alkali and 1- (2,3,5,6- tetrafluoros phenyl) indol-2-one be 1 ~ 3:1.
9. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(2)In, reaction temperature is 80~100 DEG C, and the reaction time is 5~10h.
10. the preparation method of 2- [2- (2,3,5,6- phenyl tetrafluoride amido) phenyl] acetic acid according to claim 1, its feature
It is, step(2)In, the temperature that reaction solution is down to is less than 60 DEG C;PH value after reaction solution regulation is 3~4.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201711110381.9A CN107721901A (en) | 2017-11-12 | 2017-11-12 | A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201711110381.9A CN107721901A (en) | 2017-11-12 | 2017-11-12 | A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid |
Publications (1)
Publication Number | Publication Date |
---|---|
CN107721901A true CN107721901A (en) | 2018-02-23 |
Family
ID=61214396
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201711110381.9A Pending CN107721901A (en) | 2017-11-12 | 2017-11-12 | A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107721901A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109503399A (en) * | 2018-12-29 | 2019-03-22 | 江苏天和制药有限公司 | A kind of preparation method of rofecoxib |
CN114539080A (en) * | 2022-03-02 | 2022-05-27 | 八叶草健康产业研究院(厦门)有限公司 | Preparation method of 2- (2-amino-6-chlorphenyl) -sodium acetate |
WO2023181053A1 (en) * | 2022-03-23 | 2023-09-28 | Alivira Animal Health Limited | An improved process for purification of robenacoxib |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1377337A (en) * | 1999-09-27 | 2002-10-30 | 诺瓦提斯公司 | Process for phenylacetic acid derivatives |
CN102311355A (en) * | 2011-09-26 | 2012-01-11 | 扬州天和药业有限公司 | Preparation method of rofecoxib |
-
2017
- 2017-11-12 CN CN201711110381.9A patent/CN107721901A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1377337A (en) * | 1999-09-27 | 2002-10-30 | 诺瓦提斯公司 | Process for phenylacetic acid derivatives |
CN102311355A (en) * | 2011-09-26 | 2012-01-11 | 扬州天和药业有限公司 | Preparation method of rofecoxib |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109503399A (en) * | 2018-12-29 | 2019-03-22 | 江苏天和制药有限公司 | A kind of preparation method of rofecoxib |
CN109503399B (en) * | 2018-12-29 | 2021-12-24 | 江苏天和制药有限公司 | Preparation method of Robenxib |
CN114539080A (en) * | 2022-03-02 | 2022-05-27 | 八叶草健康产业研究院(厦门)有限公司 | Preparation method of 2- (2-amino-6-chlorphenyl) -sodium acetate |
WO2023181053A1 (en) * | 2022-03-23 | 2023-09-28 | Alivira Animal Health Limited | An improved process for purification of robenacoxib |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107721901A (en) | A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid | |
CN103400983B (en) | Method for synthesizing nano lithium iron phosphate without water of crystallization through atmospheric water phase | |
CN107056675B (en) | A kind of synthetic method of silodosin and its intermediate | |
CN109503399A (en) | A kind of preparation method of rofecoxib | |
CN104817074A (en) | Process for preparing graphite intercalation compound | |
CN101323463B (en) | Production process of high pure superfine tin oxide | |
CN102584693B (en) | Preparation method for high purity 2-chlorine-3-aminopyridine hydrochloride | |
CN106008262B (en) | 4,5- dicyano -2- trifluoromethyl imidazoles, its prepare the preparation method of intermediate and its salt | |
CN105906520A (en) | Recycling method and application of L-methyldopa intermediate | |
WO2023000701A1 (en) | Method and apparatus for ultrasonic wave-assisted preparation of lithium fluorosulfonate crystal | |
CN105348134B (en) | A kind of polishing purification method of N acylamino acids | |
CN109232508B (en) | Preparation method of 1, 1-cyclohexyl diacetic anhydride | |
EP1537049A1 (en) | Method of producing crystalline lithium/vanadium oxide powder | |
CN103922959A (en) | Method for preparing intermediate diethyl acetamidomalonate through organic synthesis | |
CN102344392B (en) | Method for refining histone deacetylase (HDAC) inhibitor vorinostat | |
CN109422675B (en) | Synthesis method of novel monoamine oxidase inhibitor molabemide | |
CN110407668B (en) | Method for removing iron impurities in alkoxy aluminum | |
CN112159416B (en) | Preparation method of 4, 6-dibromo-thienofuran-1, 3-dione | |
CN100554252C (en) | A kind of preparation method of Sumatriptan Succinate | |
CN105936629B (en) | The synthetic method of body of Pramipexole dihydrochloride intermediate | |
CN110642722A (en) | Method for preparing N, N-tetramethyl decamethylene diamine | |
CN106632001A (en) | Preparation method of 4-(bromoacetyl) pyridine hydrobromide | |
CN110256196A (en) | The one-pot synthesis method of D, L- body naproxen | |
CN110054558A (en) | A kind of preparation method of 1- trifluoromethyl cyclopropane -1- formic acid | |
CN113200843B (en) | Preparation method of 5-octanoyl salicylic 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 | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180223 |