CN109535050A - A kind of preparation method of bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- - Google Patents
A kind of preparation method of bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- Download PDFInfo
- Publication number
- CN109535050A CN109535050A CN201811532346.0A CN201811532346A CN109535050A CN 109535050 A CN109535050 A CN 109535050A CN 201811532346 A CN201811532346 A CN 201811532346A CN 109535050 A CN109535050 A CN 109535050A
- Authority
- CN
- China
- Prior art keywords
- bis
- benzene
- dimethylphenyl
- sulfenyl
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/26—Separation; Purification; Stabilisation; Use of additives
- C07C319/28—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses one kind 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene preparation method, include the following steps: 2, in acid binding agent, catalyst, 1,1 '-dinaphthalene -2 are reacted to obtain 1 under 2 '-bis- diphenyl phosphine effects for 4- thiophenol dimethyl benzene and adjacent bromo-iodobenzene, bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 2-.Bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) the benzene purity is highs of 1, the 2- that the present invention is prepared, and synthetic route of the present invention is short, raw material is cheap and easy to get, and easy to operate, reaction condition is mild.
Description
Technical field
The present invention relates to chemical substance preparation technical fields, more particularly to bis- ((2, the 4- 3,5-dimethylphenyl) sulphur of 1,2- of one kind
Base) benzene preparation method.
Background technique
Hydrobromic acid Vortioxetine (Vortioxetine hydrobromide), entitled 1- [2- (2, the 4- dimethyl-benzene of chemistry
Sulfydryl)-phenyl]-piperazine hydrobromide, combined by Japanese Takede Chemical Industries Ltd and Lundbeck pharmaceutical Co. Ltd, Denmark
It develops, is listed in October, 2013 in Europe, for treating severe adult's depression.Its chemical structural formula is as follows:
Hydrobromic acid Vortioxetine is considered as a kind of novel multi-model antidepressant, and in vitro study shows that it has can
Antagonism 5-HT3,5-HT7 and 5-HT1D receptor, activates 5-HT1A receptor, and part activates 5-HT1B receptor and inhibits the transhipment of 5-HT
Function, be first antidepressant for having a variety of drug activities.
The key of hydrobromic acid Vortioxetine synthesis is the control of its impurity, therefore the impurity synthesis of hydrobromic acid Vortioxetine
Research is of great significance.Bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- are in hydrobromic acid Vortioxetine production preparation process
The impurity of generation, structural formula are as follows:
In order to guarantee the quality and safety of drug, it is necessary to qualitatively or quantitatively be divided the impurity in bulk pharmaceutical chemicals, preparation
Analysis, therefore the impurity of high-purity is provided, it is great to drug quality meaning of monitoring.At present about 1,2- bis- ((2,4- 3,5-dimethylphenyls)
Sulfenyl) benzene preparation method it is less, it is therefore desirable to the preparation side of bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene 1,2- of one kind is provided
Method provides sample for impurity research.
Summary of the invention
Technical problems based on background technology, the invention proposes bis- ((2, the 4- 3,5-dimethylphenyl) sulphur of 1,2- of one kind
Base) benzene preparation method, 1, the 2- that the present invention is prepared bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene purity is high, and the present invention
Synthetic route is short, and raw material is cheap and easy to get, easy to operate, and reaction condition is mild.
A kind of preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- proposed by the present invention, including walk as follows
It is rapid: 2,4- thiophenol dimethyl benzene and adjacent bromo-iodobenzene under acid binding agent, catalyst, 1,1 '-dinaphthalenes -2,2 '-bis- diphenyl phosphines effect into
Row reaction obtains bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-.
Preferably, reaction carries out in nitrogen atmosphere.
Preferably, acid binding agent is sodium tert-butoxide.
Preferably, catalyst is double (bis- Ya Benzyl benzylacetones) palladium.
Preferably, 2,4- thiophenol dimethyl benzene and adjacent bromo-iodobenzene are in acid binding agent, catalyst, 1,1 '-dinaphthalene -2, and 2 '-bis- two
Under phosphniline effect, reflux obtains bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- in reaction dissolvent.
Preferably, after reaction, through column chromatographic purifying.
Preferably, reaction dissolvent is toluene.
Preferably, column chromatographic eluate is petroleum ether.
Preferably, the time of reaction is 18-25h.
Preferably, the molar ratio of 2,4- thiophenol dimethyl benzene and adjacent bromo-iodobenzene is 2-3:1.
Preferably, the molar ratio of 2,4- thiophenol dimethyl benzene and acid binding agent is 1:2-4.
Preferably, the molar ratio of 2,4- thiophenol dimethyl benzene and catalyst is 1:0.01-0.02.
Preferably, 2,4- thiophenol dimethyl benzene and 1,1 '-dinaphthalene -2, the molar ratio of 2 '-bis- diphenyl phosphines are 1:0.02-
0.04。
The concrete operation step of condensation reaction are as follows: in nitrogen atmosphere, by adjacent bromo-iodobenzene, 2,4- thiophenol dimethyl benzene, urge
Agent, 1,1 '-dinaphthalene -2,2 '-bis- diphenyl phosphines, acid binding agent, reaction dissolvent mix, and reflux is cooled to room temperature, water is added to mix, mistake
Filter, takes filtrate stratification, takes organic phase, washs, dry, is spin-dried for, column chromatographs to obtain bis- ((2, the 4- 3,5-dimethylphenyl) sulphur of 1,2-
Base) benzene.
The dosage for not providing reaction dissolvent determines its dosage according to concrete operations.
It does not provide reflux temperature, is able to maintain reflux state.
Above-mentioned column chromatography is conventional technical means in the art.
Raw material of the present invention is cheap and easy to get, at low cost;Operation of the present invention is simple, and reaction condition is mild, and low energy consumption, is suitble to industry
Metaplasia produces;Synthetic route of the present invention is short, and the impurity of product is few, purity is high;It can be hydrobromic acid Vortioxetine bulk pharmaceutical chemicals and preparation
Impurity research provide high-purity impurity reference substance.
Specific embodiment
In the following, technical solution of the present invention is described in detail by specific embodiment.
Embodiment 1
The preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- of one kind, includes the following steps: in nitrogen atmosphere
In, 2.0g neighbour's bromo-iodobenzene is taken, 2.0g 2, the bis- (bis- Ya Benzyl benzylacetones of 4- thiophenol dimethyl benzene, 83mg are sequentially added) palladium, 181mg
1,1 '-dinaphthalene -2,2 '-bis- diphenyl phosphines, 2.8g sodium tert-butoxide, 100ml toluene 300r/min speed stir and evenly mix, oil bath is slow
It is warming up to reflux state, flow back 20h, is monitored and is reacted with TLC, wherein select silica GF254 lamellae, be expansion with petroleum ether
Agent;Then it is naturally cooling to room temperature, adds purified water, stirs 30min, filtering takes filtrate stratification, takes organic phase, uses quality
Score is that 15wt%NaCl aqueous solution washs organic phase 2 times, dry with anhydrous sodium sulfate, is spin-dried for organic solvent and obtains crude product, will
Crude product there are eluent 1200ml with column chromatographic purifying, be spin-dried for obtaining bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-, wherein
Column chromatographic eluate is petroleum ether, and the yield of 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene is 1.1g, purity 98.1%.
Embodiment 2
The preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- of one kind, includes the following steps: in nitrogen atmosphere
In, 1.6g neighbour's bromo-iodobenzene is taken, 2.0g 2, the bis- (bis- Ya Benzyl benzylacetones of 4- thiophenol dimethyl benzene, 83mg are sequentially added) palladium, 181mg
1,1 '-dinaphthalene -2,2 '-bis- diphenyl phosphines, 2.8g sodium tert-butoxide, 100ml toluene 300r/min speed stir and evenly mix, oil bath is slow
It is warming up to reflux state, flow back 20h, is monitored and is reacted with TLC, wherein select silica GF254 lamellae, be expansion with petroleum ether
Agent;Then it is naturally cooling to room temperature, adds purified water, stirs 30min, filtering takes filtrate stratification, takes organic phase, uses quality
Score is that 15wt%NaCl aqueous solution washs organic phase 2 times, dry with anhydrous sodium sulfate, is spin-dried for organic solvent and obtains crude product, will
Crude product there are eluent 1280ml with column chromatographic purifying, be spin-dried for obtaining bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-, wherein
Column chromatographic eluate is petroleum ether, and the yield of 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene is 1.1g%, and purity is
98.3%.
Embodiment 3
The preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- of one kind, includes the following steps: in nitrogen atmosphere
In, 1.6g neighbour's bromo-iodobenzene is taken, 2.0g 2, the bis- (bis- Ya Benzyl benzylacetones of 4- thiophenol dimethyl benzene, 167mg are sequentially added) palladium, 362mg
1,1 '-dinaphthalene -2,2 '-bis- diphenyl phosphines, 2.8g sodium tert-butoxide, 100ml toluene 300r/min speed stir and evenly mix, oil bath is slow
It is warming up to reflux state, flow back 20h, is monitored and is reacted with TLC, wherein select silica GF254 lamellae, be expansion with petroleum ether
Agent;Then it is naturally cooling to room temperature, adds purified water, stirs 30min, filtering takes filtrate stratification, takes organic phase, uses quality
Score is that 15wt%NaCl aqueous solution washs organic phase 2 times, dry with anhydrous sodium sulfate, is spin-dried for organic solvent and obtains crude product, will
Crude product there are eluent 1200ml with column chromatographic purifying, be spin-dried for obtaining bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-, wherein
Column chromatographic eluate is petroleum ether;The yield of 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene is 1.3g, purity 98.0%.
Embodiment 4
The preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- of one kind, includes the following steps: in nitrogen atmosphere
In, 2.0g neighbour's bromo-iodobenzene is taken, 2.0g 2, the bis- (bis- Ya Benzyl benzylacetones of 4- thiophenol dimethyl benzene, 167mg are sequentially added) palladium, 362mg
1,1 '-dinaphthalene -2,2 '-bis- diphenyl phosphines, 2.8g sodium tert-butoxide, 100ml toluene 300r/min speed stir and evenly mix, oil bath is slow
It is warming up to reflux state, flow back 20h, is monitored and is reacted with TLC, wherein select silica GF254 lamellae, be expansion with petroleum ether
Agent;Then it is naturally cooling to room temperature, adds purified water, stirs 30min, filtering takes filtrate stratification, takes organic phase, uses quality
Score is that 15wt%NaCl aqueous solution washs organic phase 2 times, dry with anhydrous sodium sulfate, is spin-dried for organic solvent and obtains crude product, will
Crude product there are eluent 1300ml with column chromatographic purifying, be spin-dried for obtaining bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-, wherein
Column chromatographic eluate is petroleum ether, and the yield of 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene is 1.4g, purity 98.1%.
Embodiment 5
The preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- of one kind, includes the following steps: in nitrogen atmosphere
In, 1.6g neighbour's bromo-iodobenzene is taken, 2.0g 2, the bis- (bis- Ya Benzyl benzylacetones of 4- thiophenol dimethyl benzene, 167mg are sequentially added) palladium, 362mg
1,1 '-dinaphthalene -2,2 '-bis- diphenyl phosphines, 3.5g sodium tert-butoxide, 100ml toluene 300r/min speed stir and evenly mix, oil bath is slow
It is warming up to reflux state, flow back 20h, is monitored and is reacted with TLC, wherein select silica GF254 lamellae, be expansion with petroleum ether
Agent;Then it is naturally cooling to room temperature, adds purified water, stirs 30min, filtering takes filtrate stratification, takes organic phase, uses quality
Score is that 15wt%NaCl aqueous solution washs organic phase 2 times, dry with anhydrous sodium sulfate, is spin-dried for organic solvent and obtains crude product, will
Crude product there are eluent 1400ml with column chromatographic purifying, be spin-dried for obtaining bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-, wherein
Column chromatographic eluate is petroleum ether, and the yield of 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene is 1.5g, purity 98.3%.
Embodiment 6
The preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- of one kind, includes the following steps: in nitrogen atmosphere
In, 1.37g neighbour's bromo-iodobenzene is taken, 2.0g 2, the bis- (bis- Ya Benzyl benzylacetones of 4- thiophenol dimethyl benzene, 167mg are sequentially added) palladium,
1,1 '-dinaphthalene -2 362mg, 2 '-bis- diphenyl phosphines, 5.6g sodium tert-butoxide, 100ml toluene 300r/min speed stir and evenly mix, oil
Bath is to slowly warm up to reflux state, and flow back 18h, is monitored and is reacted with TLC, wherein silica GF254 lamellae is selected, with petroleum ether
For solvent;Then it is naturally cooling to room temperature, adds purified water, stirs 30min, filtering takes filtrate stratification, takes organic phase,
It is that 15wt%NaCl aqueous solution washs organic phase 2 times with mass fraction, it is dry with anhydrous sodium sulfate, it is spin-dried for organic solvent and obtains slightly
Crude product there are eluent 1400ml with column chromatographic purifying by product, be spin-dried for obtaining bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-,
Wherein, column chromatographic eluate is petroleum ether, and the yield of 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene is 1.4g, and purity is
98.4%.
Embodiment 7
The preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- of one kind, includes the following steps: in nitrogen atmosphere
In, 1.37g neighbour's bromo-iodobenzene is taken, 2.0g 2, the bis- (bis- Ya Benzyl benzylacetones of 4- thiophenol dimethyl benzene, 167mg are sequentially added) palladium,
1,1 '-dinaphthalene -2 362mg, 2 '-bis- diphenyl phosphines, 4.2g sodium tert-butoxide, 100ml toluene 300r/min speed stir and evenly mix, oil
Bath is to slowly warm up to reflux state, and flow back 25h, is monitored and is reacted with TLC, wherein silica GF254 lamellae is selected, with petroleum ether
For solvent;Then it is naturally cooling to room temperature, adds purified water, stirs 30min, filtering takes filtrate stratification, takes organic phase,
It is that 15wt%NaCl aqueous solution washs organic phase 2 times with mass fraction, it is dry with anhydrous sodium sulfate, it is spin-dried for organic solvent and obtains slightly
Crude product there are eluent 1400ml with column chromatographic purifying by product, be spin-dried for obtaining bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-,
Wherein, column chromatographic eluate is petroleum ether, and the yield of 1,2- bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene is 1.3g, and purity is
98.5%.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto,
Anyone skilled in the art in the technical scope disclosed by the present invention, according to the technique and scheme of the present invention and its
Inventive concept is subject to equivalent substitution or change, should be covered by the protection scope of the present invention.
Claims (10)
1. one kind 1, the preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 2-, which comprises the steps of: 2,
4- thiophenol dimethyl benzene is reacted under acid binding agent, catalyst, 1,1 '-dinaphthalenes -2,2 '-bis- diphenyl phosphines effect with adjacent bromo-iodobenzene
Obtain bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2-.
2. the preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 1, which is characterized in that anti-
It should be carried out in nitrogen atmosphere.
3. the preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 1 or claim 2, feature exist
In acid binding agent is sodium tert-butoxide.
4. the preparation method of any one of -3 bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 1, special
Sign is that catalyst is double (bis- Ya Benzyl benzylacetones) palladium.
5. the preparation method of any one of -4 bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 1, special
Sign is that 2,4- thiophenol dimethyl benzenes and adjacent bromo-iodobenzene are in acid binding agent, catalyst, 1,1 '-dinaphthalene -2,2 '-bis- diphenyl phosphine effects
Under, reflux is reacted to obtain bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- in reaction dissolvent.
6. the preparation method of any one of -5 bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 1, special
Sign is, after reaction, through column chromatographic purifying.
7. the preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 5, which is characterized in that anti-
Answering solvent is toluene.
8. the preparation method of bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 6, which is characterized in that column
Chromatographic eluate is petroleum ether.
9. the preparation method of any one of -8 bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 1, special
Sign is that the time of reaction is 18-25h.
10. the preparation method of any one of -9 bis- ((2, the 4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- according to claim 1, special
Sign is that the molar ratio of 2,4- thiophenol dimethyl benzenes and adjacent bromo-iodobenzene is 2-3:1;Preferably, 2,4- thiophenol dimethyl benzene with tie up
The molar ratio of sour agent is 1:2-4;Preferably, the molar ratio of 2,4- thiophenol dimethyl benzene and catalyst is 1:0.01-0.02;It is preferred that
Ground, 2,4- thiophenol dimethyl benzenes and 1,1 '-dinaphthalene -2, the molar ratio of 2 '-bis- diphenyl phosphines are 1:0.02-0.04.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811532346.0A CN109535050A (en) | 2018-12-14 | 2018-12-14 | A kind of preparation method of bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811532346.0A CN109535050A (en) | 2018-12-14 | 2018-12-14 | A kind of preparation method of bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- |
Publications (1)
Publication Number | Publication Date |
---|---|
CN109535050A true CN109535050A (en) | 2019-03-29 |
Family
ID=65856220
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811532346.0A Pending CN109535050A (en) | 2018-12-14 | 2018-12-14 | A kind of preparation method of bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109535050A (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101472906A (en) * | 2006-06-16 | 2009-07-01 | H.隆德贝克有限公司 | 1- [2- (2, 4-dimethylphenylsulfanyl) -phenyl] piperazine as a compound with combined serotonin reuptake, 5-HT3 and 5-HT1A activity for the treatment of cognitive impairment |
CN106556663A (en) * | 2015-09-30 | 2017-04-05 | 成都弘达药业有限公司 | A kind of detection method of 1- [2- (2,4- dimethylphenylsulfanyls) phenyl] piperazines or its salt |
US20180030008A1 (en) * | 2015-02-25 | 2018-02-01 | Lupin Limited | Process for the preparation of vortioxetine |
CN108017595A (en) * | 2017-12-20 | 2018-05-11 | 安徽源久源科技有限公司 | A kind of preparation method of 1- [2- (2,5- dimethyl benzenes sulfenyl) phenyl] piperazine |
-
2018
- 2018-12-14 CN CN201811532346.0A patent/CN109535050A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101472906A (en) * | 2006-06-16 | 2009-07-01 | H.隆德贝克有限公司 | 1- [2- (2, 4-dimethylphenylsulfanyl) -phenyl] piperazine as a compound with combined serotonin reuptake, 5-HT3 and 5-HT1A activity for the treatment of cognitive impairment |
US20180030008A1 (en) * | 2015-02-25 | 2018-02-01 | Lupin Limited | Process for the preparation of vortioxetine |
CN106556663A (en) * | 2015-09-30 | 2017-04-05 | 成都弘达药业有限公司 | A kind of detection method of 1- [2- (2,4- dimethylphenylsulfanyls) phenyl] piperazines or its salt |
CN108017595A (en) * | 2017-12-20 | 2018-05-11 | 安徽源久源科技有限公司 | A kind of preparation method of 1- [2- (2,5- dimethyl benzenes sulfenyl) phenyl] piperazine |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Panke et al. | A practical approach of continuous processing to high energetic nitration reactions in microreactors | |
CN107903211B (en) | Preparation method of 3-halogenated-2, 3-dihydro-4-quinolinone | |
KR102230628B1 (en) | Vortioxetine manufacturing process | |
Ahmed-Omer et al. | Preparation of fluoxetine by multiple flow processing steps | |
CN103641722B (en) | A kind of production method of adjacent nitro bromobenzyl | |
CN109761862A (en) | A kind of synthetic method of β-carbonyl sulfone compound | |
CN107337676A (en) | A kind of support method replaces the preparation method of cloth initiation material | |
CN109020881A (en) | A kind of Ah pa replaces the preparation method of Buddhist nun | |
CN105566215B (en) | A kind of Rui Gefeini preparation method | |
CN104292183A (en) | Preparation method of antidepressant drug Vortioxetine | |
CN109535050A (en) | A kind of preparation method of bis- ((2,4- 3,5-dimethylphenyl) sulfenyl) benzene of 1,2- | |
Hirakawa et al. | A chronicle review: Regioselective synthesis of trifluoromethyl group containing allylic amines using palladium-catalyzed allylic amination pathway | |
Yang et al. | Copper-mediated trifluoromethylation of diaryliodonium salts with difluoromethyltriflate | |
CN109438390A (en) | A kind of synthetic method of hydrobromic acid Vortioxetine impurity | |
CN110272403A (en) | A method of carbamate of the synthesis containing chroman ring and trifluoromethyl | |
Zhang et al. | Nickel-catalyzed reductive cross-coupling of benzyl halides with aryl halides | |
Jiang et al. | Reactions of methylenecyclopropanes and vinylidenecyclopropanes with N-fluorodibenzenesulfonimide | |
Halder et al. | Palladium-Catalyzed Aminocarbonylation of Isoquinolines Utilizing Chloroform-COware Chemistry | |
CN106866425B (en) | A kind of green synthesis method of bromo aromatic amine and alpha-brominated aromatic ketone | |
Zisopoulou et al. | Environmentally Benign Large-Scale Synthesis of a Precursor to Vortioxetine | |
Guido et al. | Pentaerythritol tetrakis (4-iodo-2, 3, 5, 6-tetrafluorophenyl) ether: a tecton for the self-assembly of double strand 1D infinite chains | |
CN104311377B (en) | A kind of synthetic method of biphenyl compound | |
CN107915694A (en) | 1 [2 (2,4 3,5-dimethylphenyl sulfydryl) phenyl] piperazine hydrochloride and preparation method thereof | |
CN113329994B (en) | Method for continuously preparing 5-cyanodiol | |
Gohari et al. | Novel enantioselective synthesis of (S)-ketamine using chiral auxiliary and precursor Mannich base |
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: 20190329 |
|
RJ01 | Rejection of invention patent application after publication |