CN105061253A - Preparation method of bromine-containing azide - Google Patents
Preparation method of bromine-containing azide Download PDFInfo
- Publication number
- CN105061253A CN105061253A CN201510427282.8A CN201510427282A CN105061253A CN 105061253 A CN105061253 A CN 105061253A CN 201510427282 A CN201510427282 A CN 201510427282A CN 105061253 A CN105061253 A CN 105061253A
- Authority
- CN
- China
- Prior art keywords
- reaction
- compound
- xylol
- mixture
- bromo
- 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
Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of 3-bromophenyl azide1-(3-azidopropyl)-3-bromo-4-ethoxybenzene. 3-(3-bromo-4-ethoxyphenyl)acrylic acid is used as a starting material, a target product 5 is obtained through reduction, hydrogenation, Ms (methylsulfonyl) loading and azidation reactions, and the product is used as a template micro-molecule for synthesis of various compound libraries.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, particularly the preparation method of the bromo-4-phenetole of a kind of 3-bromophenyl triazo-compound 1-(3-Azidopropyl)-3-.
Technical background
The bromo-4-phenetole of compound 1-(3-Azidopropyl)-3-, structural formula is:
This compound 3-bromophenyl triazo-compound 1-(3-Azidopropyl)-3-bromo-4-phenetole and relevant derivative have widespread use in pharmaceutical chemistry and organic synthesis.The synthesis of current 3-bromophenyl triazo-compound 1-(3-Azidopropyl)-3-bromo-4-phenetole is comparatively difficult.Therefore, need exploitation raw material to be easy to get, easy to operate, reaction is easy to control, the synthetic method that overall yield is suitable.
Summary of the invention
The invention discloses the preparation method of the bromo-4-phenetole of a kind of 3-bromophenyl triazo-compound 1-(3-Azidopropyl)-3-, with 3-(the bromo-4-ethoxyl phenenyl of 3-) vinylformic acid for starting raw material, obtain target product 5 through reduction, hydrogenation, upper Ms, azido reaction, synthetic route as shown in Figure 1.Synthesis step is as follows:
(1) 3-(the bromo-4-ethoxyl phenenyl of 3-) vinylformic acid is starting raw material, obtains 2 through reduction reaction,
(2) carry out hydrogenation reaction 2, obtain 3,
(3) carry out upper Ms 3 and be obtained by reacting 4,
(4) carry out azido reaction 4 and obtain 5,
One preferred embodiment in, described reduction reaction is prepared compound 2 reagent used and is selected from Lithium Aluminium Hydride; Described hydrogenation reaction is prepared compound 3 reagent used and is selected from palladium carbon; Described upper Ms reacts the reagent preparing compound 4 used and is selected from triethylamine; The reagent that described azido reaction prepares compound 5 used is selected from sodiumazide.
One preferred embodiment in, the solvent that described reduction reaction prepares compound 2 used is selected from tetrahydrofuran (THF); Described hydrogenation reaction prepares compound 3 solvent selected from methanol used; Described upper Ms reacts the solvent preparing compound 4 used and is selected from methylene bromide; The solvent that described azido reaction prepares compound 5 used is selected from DMF.
One preferred embodiment in, described reduction reaction prepare compound 2 temperature of reaction used be 0 DEG C to room temperature; It is room temperature that described hydrogenation reaction prepares compound 3 temperature used; Described upper Ms reaction prepare compound 4 temperature used be 0 DEG C to room temperature; It is room temperature that described azido reaction prepares compound 5 temperature used.
The present invention relates to the preparation method of the bromo-4-phenetole of a kind of 3-bromophenyl triazo-compound 1-(3-Azidopropyl)-3-, there is no other Patents bibliographical informations at present.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of the bromo-4-phenetole of compound 1-(3-Azidopropyl)-3-.
The present invention is further described by the following embodiment, and these descriptions are not be further limited content of the present invention.One skilled in the art will understand that the equivalent replacement that technical characteristic of the present invention is done, or improve accordingly, still belong within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 3-(the bromo-4-ethoxyl phenenyl of 3-) third-2-alkene-1-alcohol
16g3-(the bromo-4-ethoxyl phenenyl of 3-) vinylformic acid is joined in 200ml tetrahydrofuran (THF), be cooled to 0 DEG C, slowly add 6g Lithium Aluminium Hydride in batches, stirred overnight at room temperature, adds water and ethyl acetate, extraction separatory, collect organic phase, drying, concentrated, obtain 7g3-(the bromo-4-ethoxyl phenenyl of 3-) third-2-alkene-1-alcohol.
(2) synthesis of 3-(the bromo-4-ethoxyl phenenyl of 3-) the third-1-alcohol
7g3-(the bromo-4-ethoxyl phenenyl of 3-) third-2-alkene-1-alcohol is joined in 40ml methyl alcohol, adds 0.5g10% palladium carbon, pass into hydrogen, stirred overnight at room temperature, filters, and collects filtrate, concentrated, obtain 5g3-(the bromo-4-ethoxyl phenenyl of 3-) the third-1-alcohol.
(3) synthesis of 3-(the bromo-4-ethoxyl phenenyl of 3-) propyl Methanesulfonate
5g3-(the bromo-4-ethoxyl phenenyl of 3-) the third-1-alcohol is joined in 50ml methylene bromide, add 3g triethylamine, be cooled to 0 DEG C, add 2.9gMsCl, stirring at room temperature 2 hours, add water again, extraction separatory, collects organic phase, dry, concentrated, on residuum, silicagel column is separated to obtain 3.4g3-(the bromo-4-ethoxyl phenenyl of 3-) propyl Methanesulfonate.
(4) synthesis of the bromo-4-phenetole of 1-(3-Azidopropyl)-3-
3g3-(the bromo-4-ethoxyl phenenyl of 3-) propyl Methanesulfonate is joined 30mlN, in dinethylformamide, add 4g sodiumazide, stirring at room temperature 6 hours, adds water and ethyl acetate, extraction separatory, collect organic phase, drying, concentrated, on residuum, silicagel column is separated to obtain the bromo-4-phenetole of 2.5g1-(3-Azidopropyl)-3-.
Claims (5)
1. the preparation method of the bromo-4-phenetole of a kind of 3-bromophenyl triazo-compound 1-(3-Azidopropyl)-3-, with 3-(the bromo-4-ethoxyl phenenyl of 3-) vinylformic acid for starting raw material, obtain target product 5 through reduction, hydrogenation, upper Ms, azido reaction, synthetic route is as follows:
2. method according to claim 1, it is characterized by 4 described step reactions is,
(1) 3-(the bromo-4-ethoxyl phenenyl of 3-) vinylformic acid is starting raw material, obtains 2 through reduction reaction,
(2) carry out hydrogenation reaction 2, obtain 3,
(3) carry out upper Ms 3 and be obtained by reacting 4,
(4) carry out azido reaction 4 and obtain 5,
3. according to the method for claim 1-2, it is characterized in that, described reduction reaction is prepared compound 2 reagent used and is selected from one or both mixture in borine, Lithium Aluminium Hydride; Described hydrogenation reaction is prepared compound 3 reagent used and is selected from the mixture of one or more in palladium carbon, palladium hydroxide, Raney's nickel; Described upper Ms reaction is prepared compound 4 reagent used and is selected from the mixture of one or more in triethylamine, pyridine, salt of wormwood, sodium hydroxide; The reagent that described azido reaction prepares compound 5 used is selected from sodiumazide.
4. according to the method for claim 1-2, it is characterized in that, described reduction reaction is prepared compound 2 solvent used and is selected from tetrahydrofuran (THF), methylene bromide, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, acetonitrile; Described hydrogenation reaction prepares compound 3 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene bromide, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, acetonitrile; Compound 4 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, acetonitrile, tetrahydrofuran (THF), dioxane, methylene bromide, methenyl bromide, toluene, o-Xylol, p-Xylol, m-xylene, N are prepared in described upper Ms reaction, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide; Described azido reaction prepares compound 5 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene bromide, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, acetonitrile.
5. according to the method for claim 1-2, it is characterized in that, it is 0 DEG C of reflux temperature to solvent that described reduction reaction prepares compound 2 temperature of reaction used; It is room temperature that described hydrogenation reaction prepares compound 3 temperature used; It is 0 DEG C of reflux temperature to solvent that compound 4 temperature used is prepared in described upper Ms reaction; It is room temperature that described azido reaction prepares compound 5 temperature used.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510427282.8A CN105061253A (en) | 2015-07-20 | 2015-07-20 | Preparation method of bromine-containing azide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510427282.8A CN105061253A (en) | 2015-07-20 | 2015-07-20 | Preparation method of bromine-containing azide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105061253A true CN105061253A (en) | 2015-11-18 |
Family
ID=54490826
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510427282.8A Pending CN105061253A (en) | 2015-07-20 | 2015-07-20 | Preparation method of bromine-containing azide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105061253A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106883140A (en) * | 2017-02-26 | 2017-06-23 | 长沙深橙生物科技有限公司 | A kind of preparation method containing azido micromolecular compound |
| CN108117514A (en) * | 2016-11-29 | 2018-06-05 | 湖南华腾制药有限公司 | A kind of preparation method of pyridine azido compound |
-
2015
- 2015-07-20 CN CN201510427282.8A patent/CN105061253A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108117514A (en) * | 2016-11-29 | 2018-06-05 | 湖南华腾制药有限公司 | A kind of preparation method of pyridine azido compound |
| CN106883140A (en) * | 2017-02-26 | 2017-06-23 | 长沙深橙生物科技有限公司 | A kind of preparation method containing azido micromolecular compound |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104230853B (en) | A kind of preparation method of (p-methylphenyl) methylamine-N-ethylmorpholine hydrochloride | |
| CN104262257A (en) | Preparation method of pyrazole derivative | |
| CN104592198A (en) | Method for preparing 2-methyl-5-(piperidin-4-yl) pyrimidine | |
| CN105017066A (en) | Chlorinated azide preparation method | |
| CN105001118A (en) | Method for preparing iodine-containing azido compound | |
| CN105001117A (en) | Method for synthesizing chlorine-containing azide compound | |
| CN104817515A (en) | Preparation method of benzene substituent oxadiazole compound | |
| CN105061253A (en) | Preparation method of bromine-containing azide | |
| CN105061254A (en) | Synthetic method of bromine-containing azide | |
| CN105130841A (en) | Preparation method of 3-iodophenyl azide compound | |
| CN104860910A (en) | Preparation method of 8-fluoropyran derivative | |
| CN104844549A (en) | Preparation method of 7 - bromine pyran derivatives | |
| CN103980120A (en) | Synthesis method of D,L-danshensu isopropyl ester | |
| CN104326977A (en) | Preparation method of 6,7-diethyl-4-hydroxyquinoline | |
| CN103694182B (en) | A kind of preparation method of quinoxaline compound | |
| CN105153020A (en) | Preparation method for aromatic azide | |
| CN105152965A (en) | Preparation method for 2-iodophenyl azide | |
| CN105152966A (en) | Preparation method for azide | |
| CN104370835A (en) | Preparation method of triazole derivative | |
| CN104592109A (en) | Method for preparing 8-bromoquinoline derivative | |
| CN104447567B (en) | A kind of preparation method of 1 substituted benzimidazole derivant | |
| CN104292213A (en) | Preparation method of pyrimidine derivative | |
| CN104262265B (en) | A kind of preparation method of tetrahydro quinazoline derivative | |
| CN104402859A (en) | Preparation method for 3-(piperidine-4-yl)-pyridazine | |
| CN104557672B (en) | A kind of preparation method of 1 substituted piperidine derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20151118 |