CN107698547A - A kind of preparation method of pyran derivate - Google Patents
A kind of preparation method of pyran derivate Download PDFInfo
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- CN107698547A CN107698547A CN201610647638.3A CN201610647638A CN107698547A CN 107698547 A CN107698547 A CN 107698547A CN 201610647638 A CN201610647638 A CN 201610647638A CN 107698547 A CN107698547 A CN 107698547A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
Abstract
The invention discloses a kind of methoxyl group N methyl 3 of pyran derivate 5, the preparation method of the amine of 4 dihydro 2H pyrans 3, using 2 (hydroxy phenyl of 6 methoxyl group 2) methyl acetates as initiation material, target product 5 is obtained by etherificate, cyclization, decarboxylation, ammonification reduction 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 pyran derivate 5- methoxies
The preparation method of base-N- methyl -3,4- dihydro -2H- pyrans -3- amine.
Technical background
Compound 5- methoxy-. N-methyl -3,4- dihydro -2H- pyrans -3- amine, structural formula are：
This compound 5- methoxy-. N-methyl -3,4- dihydro -2H- pyrans -3- amine and the derivative of correlation are in pharmaceutical chemistry
And there is extensive use in organic synthesis.The synthesis of 5- methoxy-. N-methyls -3,4- dihydros -2H- pyrans -3- amine at present is more
It is difficult.Therefore it is easy to get, it is necessary to develop a raw material, it is easy to operate, react easily controllable, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses a kind of preparation of pyran derivate 5- methoxy-. N-methyls -3,4- dihydros -2H- pyrans -3- amine
Method, using 2- (6- methoxyl group -2- hydroxy phenyls) methyl acetate as initiation material, reduced by etherificate, cyclization, decarboxylation, ammonification
Reaction obtains target product 5, and synthesis step is as follows：
(1), as initiation material, 2 are obtained by etherification reaction using 2- (6- methoxyl group -2- hydroxy phenyls) methyl acetate,
(2) ring closure reaction is carried out 2, obtains 3,
(3) 3 progress decarboxylic reactions are obtained 4,
(4) 4 progress ammonification reduction reactions are obtained 5,
In a preferred embodiment, the reagent used in described etherification reaction prepare compound 2 is selected from bromoacetic acid second
Ester；Reagent used in described ring closure reaction prepare compound 3 is selected from caustic alcohol；The described institute of decarboxylic reaction prepare compound 4
Reducing agent is selected from sodium hydroxide；Reducing agent used in described ammonification reduction reaction prepare compound 5 is selected from methylamine hydrochloric acid
Salt.
In a preferred embodiment, the solvent used in described etherification reaction prepare compound 2 is selected from N, N- diformazans
Base formamide；Solvent used in described ring closure reaction prepare compound 3 is selected from ethanol；Described decarboxylic reaction prepare compound
Solvent used in 4 is selected from N,N-dimethylformamide；Solvent used in described ammonification reduction reaction prepare compound 5 is selected from first
Alcohol.
In a preferred embodiment, the reaction temperature used in described etherification reaction prepare compound 2 is solvent
Reflux temperature；Temperature used in described ring closure reaction prepare compound 3 is 0 DEG C of reflux temperature to solvent；Described decarboxylation
Temperature used in reaction prepare compound 4 is the reflux temperature of solvent；Used in described ammonification reduction reaction prepare compound 5
Temperature is room temperature.
The present invention relates to a kind of preparation side of pyran derivate 5- methoxy-. N-methyls -3,4- dihydros -2H- pyrans -3- amine
Method, 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 2- (6- methoxyl group -2- phenoxyethanoic acids ethyl ester) ethyl acetate
17g 2- (6- methoxyl group -2- hydroxy phenyls) methyl acetate is added in 130ml DMFs,
15g bromoacetates and 12g potassium carbonate are added, heating stirring backflow, is cooled to room temperature, adds water and ethyl acetate, extraction point
Liquid, organic phase is collected, dried, concentration, obtain 10g 2- (6- methoxyl group -2- phenoxyethanoic acids ethyl ester) ethyl acetate.
(2) synthesis of 5- methoxyl groups -3- oxos -3,4- dihydros -2H- chromene -4- Ethyl formates
10g 2- (6- methoxyl group -2- phenoxyethanoic acids ethyl ester) ethyl acetate is added in 70ml ethanol, is cooled to 0
DEG C, 8g caustic alcohols are added, heating stirring back flow reaction 3 hours, room temperature is cooled down, concentration, adds water and ethyl acetate extraction liquid separation,
Organic phase is collected, dries, is concentrated to give 7g 5- methoxyl group -3- oxo -3,4- dihydro -2H- chromene -4- Ethyl formates.
(3) synthesis of 5- methoxyl groups -2H- chromenes -3 (4H) -one
7g 5- methoxyl group -3- oxo -3,4- dihydro -2H- chromene -4- Ethyl formates are added to 80mlN, N- dimethyl
In formamide, 5g sodium hydroxides are added, stirring 24 hours is heated to reflux, filtering, adds water and ethyl acetate, extract liquid separation,
Organic phase is collected, is dried, is concentrated, silica gel post separation obtains (4H) -one of 4g 5- methoxyl group -2H- chromenes -3 on residue.
(4) synthesis of 5- methoxy-. N-methyls -3,4- dihydros -2H- pyrans -3- amine
(4H) -one of 4g 5- methoxyl group -2H- chromenes -3 is added in 30ml methanol, adds 3g methylamine hydrochlorides, room temperature
Stirring 20 hours, adds 4g sodium borohydrides, is stirred at room temperature 3 hours, filters, and adds water and ethyl acetate, extracts liquid separation, receives
Collect organic phase, dry, concentration, on residue silica gel post separation obtain 2.1g 5- methoxy-. N-methyl -3,4- dihydro -2H- pyrans -
3- amine.
Claims (5)
- A kind of 1. preparation method of pyran derivate 5- methoxy-. N-methyls -3,4- dihydro -2H- pyrans -3- amine, with 2- (6- first Epoxide -2- hydroxy phenyls) methyl acetate is initiation material, obtain target production by etherificate, cyclization, decarboxylation, ammonification reduction reaction Thing 5, synthetic route is as follows：
- 2. method according to claim 1, it is characterized in that described 4 steps reaction is,(1), as initiation material, 2 are obtained by etherification reaction using 2- (6- methoxyl group -2- hydroxy phenyls) methyl acetate,(2) ring closure reaction is carried out 2, obtains 3,(3) 3 progress decarboxylic reactions are obtained 4,(4) 4 progress ammonification reduction reactions are obtained 5,
- 3. method according to claim 1, it is characterised in that the reagent used in described etherification reaction prepare compound 2 is selected from Bromoacetate；Reagent used in described ring closure reaction prepare compound 3 is selected from caustic alcohol；Described decarboxylic reaction preparationization One or more of mixtures of the reducing agent in sodium hydroxide, potassium hydroxide, potassium carbonate used in compound 4；Described ammonia Change the reducing agent used in reduction reaction prepare compound 5 and be selected from methylamine hydrochloride.
- 4. method according to claim 1, it is characterised in that the solvent used in described etherification 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 ring closure 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 decarboxylic reaction preparationization 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 ammonification reduction reaction prepare compound 5 is selected from methanol, ethanol, positive third Alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, One or more of mixtures in DMAC N,N' dimethyl acetamide, acetonitrile.
- 5. method according to claim 1, it is characterised in that the reaction temperature used in described etherification reaction prepare compound 2 It is the reflux temperature of solvent；Temperature used in described ring closure reaction prepare compound 3 is 0 DEG C of reflux temperature to solvent；Institute The temperature used in decarboxylic reaction prepare compound 4 stated is reflux temperature of the room temperature to solvent；Described ammonification reduction reaction system Temperature used in standby compound 5 is room temperature.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106995426A (en) * | 2017-05-31 | 2017-08-01 | 湖南华腾制药有限公司 | A kind of preparation method of 5 chlorine pyran derivate |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926775A (en) * | 2015-05-07 | 2015-09-23 | 湖南华腾制药有限公司 | Preparation method of fluorine-containing pyran derivative |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926775A (en) * | 2015-05-07 | 2015-09-23 | 湖南华腾制药有限公司 | Preparation method of fluorine-containing pyran derivative |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106995426A (en) * | 2017-05-31 | 2017-08-01 | 湖南华腾制药有限公司 | A kind of preparation method of 5 chlorine pyran derivate |
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