CN107043335A - A kind of preparation method of 2 fluorophenyl azido compound - Google Patents
A kind of preparation method of 2 fluorophenyl azido compound Download PDFInfo
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- CN107043335A CN107043335A CN201710401080.5A CN201710401080A CN107043335A CN 107043335 A CN107043335 A CN 107043335A CN 201710401080 A CN201710401080 A CN 201710401080A CN 107043335 A CN107043335 A CN 107043335A
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- xylene
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- 0 COc(ccc(CCC*)c1)c1F Chemical compound COc(ccc(CCC*)c1)c1F 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
- C07C247/08—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated
- C07C247/10—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated and containing rings
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation method of the methoxybenzene of 2 fluorine of 2 fluorophenyl azido compound 4 (3 Azidopropyl) 1, using 3 (methoxyphenyl of 3 fluorine 4) acrylic acid as initiation material, target product 5 is obtained by reduction, hydrogenation, upper Ms, azido reaction, product of the present invention synthesizes diversified compound library as template small molecule.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, more particularly to a kind of 2- fluorophenyls azido compound
The preparation method of the fluoro- 1- methoxybenzenes of 4- (3- Azidopropyls) -2-.
Technical background
The fluoro- 1- methoxybenzenes of compound 4- (3- Azidopropyls) -2-, structural formula is：
This compound 2- fluorophenyl azido compounds fluoro- 1- methoxybenzenes of 4- (3- Azidopropyls) -2- and correlation spread out
Biology has extensive use in pharmaceutical chemistry and organic synthesis.Current 2- fluorophenyl azido compound 4- (3- azidos third
Base) the fluoro- 1- methoxybenzenes of -2- synthesis it is more difficult.It is easy to get accordingly, it would be desirable to develop a raw material, easy to operate, reaction is easy to
Control, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses a kind of fluoro- 1- methoxybenzenes of 2- fluorophenyls azido compound 4- (3- Azidopropyls) -2-
Preparation method, it is anti-by reduction, hydrogenation, upper Ms, Azide as initiation material using 3- (the fluoro- 4- methoxyphenyls of 3-) acrylic acid
Target product 5 should be obtained, synthesis step is as follows：
(1) 3- (the fluoro- 4- methoxyphenyls of 3-) acrylic acid is initiation material, and 2 are obtained by reduction reaction,
(2) hydrogenation reaction is carried out 2, obtains 3,
(3) upper Ms reactions are carried out 3 and obtain 4,
(4) 4 progress azido reactions are obtained 5,
In a preferred embodiment, the reagent used in described reduction reaction prepare compound 2 is selected from Lithium Aluminium Hydride
In；Reagent used in described hydrogenation reaction prepare compound 3 is selected from palladium carbon；Used in described upper Ms reaction prepare compounds 4
Reagent be selected from triethylamine；Reagent used in described azido reaction prepare compound 5 is selected from sodium azide.
In a preferred embodiment, the solvent used in described reduction reaction prepare compound 2 is selected from tetrahydrofuran；
Solvent used in described hydrogenation reaction prepare compound 3 is selected from methanol；It is molten used in described upper Ms reaction prepare compounds 4
Agent is selected from dichloromethane；Solvent used in described azido reaction prepare compound 5 is selected from N,N-dimethylformamide.
In a preferred embodiment, the reaction temperature used in described reduction reaction prepare compound 2 is 0 DEG C to room
Temperature；Temperature used in described hydrogenation reaction prepare compound 3 is room temperature；Used in described upper Ms reaction prepare compounds 4
Temperature is 0 DEG C to room temperature；Temperature used in described azido reaction prepare compound 5 is room temperature.
The present invention relates to a kind of system of the fluoro- 1- methoxybenzenes of 2- fluorophenyls azido compound 4- (3- Azidopropyls) -2-
Preparation Method, is reported currently without other Patents documents.
The present invention is further described by the following embodiment, and these descriptions are not present invention to be made into one
The restriction of step.It should be understood by those skilled in the art that the equivalent substitution made to the technical characteristic of the present invention, or change accordingly
Enter, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 3- (the fluoro- 4- methoxyphenyls of 3-) propyl- 2- alkene -1- alcohol
15g 3- (the fluoro- 4- methoxyphenyls of 3-) acrylic acid is added in 200ml tetrahydrofurans, 0 DEG C is cooled to, in batches
6g Lithium Aluminium Hydrides are slowly added to, are stirred overnight at room temperature, water and ethyl acetate are added, extraction point liquid is collected organic phase, dried, dense
Contracting, obtains 8g 3- (the fluoro- 4- methoxyphenyls of 3-) propyl- 2- alkene -1- alcohol.
(2) synthesis of 3- (the fluoro- 4- methoxyphenyls of 3-) propyl- 1- alcohol
8g 3- (the fluoro- 4- methoxyphenyls of 3-) propyl- 2- alkene -1- alcohol is added in 40ml methanol, 0.5g 10% is added
Palladium carbon, is passed through hydrogen, is stirred overnight at room temperature, filtering, collects filtrate, and concentration obtains 6g 3- (the fluoro- 4- methoxyphenyls of 3-) propyl-
1- alcohol.
(3) synthesis of 3- (the fluoro- 4- methoxyphenyls of 3-) propyl Methanesulfonate
5g 3- (the fluoro- 4- methoxyphenyls of 3-) propyl- 1- alcohol is added in 50ml dichloromethane, 3g triethylamines are added, it is cold
But to 0 DEG C, 2.9g MsCl is added, are stirred at room temperature 2 hours, add water, extraction point liquid is collected organic phase, dried, concentrate, remains
Silica gel post separation obtains 3.6g 3- (the fluoro- 4- methoxyphenyls of 3-) propyl Methanesulfonate on excess.
(4) synthesis of the fluoro- 1- methoxybenzenes of 4- (3- Azidopropyls) -2-
3g 3- (the fluoro- 4- methoxyphenyls of 3-) propyl Methanesulfonate is added in 30ml DMFs,
4g sodium azide is added, is stirred at room temperature 6 hours, water and ethyl acetate is added, extraction point liquid is collected organic phase, dried, concentration,
Silica gel post separation obtains the fluoro- 1- methoxybenzenes of 2.6g 4- (3- Azidopropyls) -2- on residue.
Claims (5)
1. the preparation method of the fluoro- 1- methoxybenzenes of a kind of 2- fluorophenyls azido compound 4- (3- Azidopropyls) -2-, with 3-
(the fluoro- 4- methoxyphenyls of 3-) acrylic acid is initiation material, and target product is obtained by reduction, hydrogenation, upper Ms, azido reaction
5, synthetic route is as follows：
2. method according to claim 1, it is characterized in that described 4 steps reaction is,
(1) 3- (the fluoro- 4- methoxyphenyls of 3-) acrylic acid is initiation material, and 2 are obtained by reduction reaction,
(2) hydrogenation reaction is carried out 2, obtains 3,
(3) upper Ms reactions are carried out 3 and obtain 4,
(4) 4 progress azido reactions are obtained 5,
3. method according to claim 1, it is characterised in that the reagent used in described reduction reaction prepare compound 2 is selected from
The mixture of one or both of borine, Lithium Aluminium Hydride；Reagent used in described hydrogenation reaction prepare compound 3 is selected from palladium
One or more of mixtures in carbon, palladium dydroxide, Raney's nickel；Reagent used in described upper Ms reaction prepare compounds 4
One or more of mixtures in triethylamine, pyridine, potassium carbonate, sodium hydroxide；Described azido reaction preparationization
Reagent used in compound 5 is selected from sodium azide.
4. method according to claim 1, it is characterised in that the solvent used in described reduction reaction prepare compound 2 is selected from
Tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, N, N- dimethyl
One or more of mixtures in acetamide, acetonitrile；Solvent used in described hydrogenation reaction prepare compound 3 is selected from first
Alcohol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N, N-
One or more of mixtures in dimethylformamide, DMAC N,N' dimethyl acetamide, acetonitrile；Described upper Ms reaction preparationizations
Solvent used in compound 4 is selected from methanol, ethanol, normal propyl alcohol, isopropanol, acetonitrile, tetrahydrofuran, dioxane, dichloromethane, three
In chloromethanes, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide
One or more of mixtures；Solvent used in described azido reaction prepare compound 5 be selected from methanol, ethanol, normal propyl alcohol,
Isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, N,
One or more of mixtures in N- dimethyl acetamides, acetonitrile.
5. method according to claim 1, it is characterised in that the reaction temperature used in described reduction reaction prepare compound 2
It is 0 DEG C of reflux temperature to solvent；Temperature used in described hydrogenation reaction prepare compound 3 is room temperature；Described upper Ms is anti-
It is 0 DEG C of reflux temperature to solvent to answer the temperature used in prepare compound 4；Used in described azido reaction prepare compound 5
Temperature be room temperature.
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| CN201710401080.5A CN107043335A (en) | 2017-05-31 | 2017-05-31 | A kind of preparation method of 2 fluorophenyl azido compound |
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| CN201710401080.5A CN107043335A (en) | 2017-05-31 | 2017-05-31 | A kind of preparation method of 2 fluorophenyl azido compound |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1438996A (en) * | 2000-05-31 | 2003-08-27 | 沃尼尔·朗伯公司 | Bicyclic cyclohexylamines and their use NMDA receptor antogonists |
| CN105017066A (en) * | 2015-07-20 | 2015-11-04 | 湖南华腾制药有限公司 | Chlorinated azide preparation method |
| CN105130841A (en) * | 2015-07-20 | 2015-12-09 | 湖南华腾制药有限公司 | Preparation method of 3-iodophenyl azide compound |
-
2017
- 2017-05-31 CN CN201710401080.5A patent/CN107043335A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1438996A (en) * | 2000-05-31 | 2003-08-27 | 沃尼尔·朗伯公司 | Bicyclic cyclohexylamines and their use NMDA receptor antogonists |
| CN105017066A (en) * | 2015-07-20 | 2015-11-04 | 湖南华腾制药有限公司 | Chlorinated azide preparation method |
| CN105130841A (en) * | 2015-07-20 | 2015-12-09 | 湖南华腾制药有限公司 | Preparation method of 3-iodophenyl azide compound |
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Application publication date: 20170815 |