CN105017136A - 2-bromo-3-methoxypyridine preparation method - Google Patents
2-bromo-3-methoxypyridine preparation method Download PDFInfo
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- CN105017136A CN105017136A CN201510438913.6A CN201510438913A CN105017136A CN 105017136 A CN105017136 A CN 105017136A CN 201510438913 A CN201510438913 A CN 201510438913A CN 105017136 A CN105017136 A CN 105017136A
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- bromo
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- pyridone
- sodium hydroxide
- methoxy pyridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The present invention belongs to the technical field of organic synthesis, and in particular relates to a 2-bromo-3-methoxypyridine preparation method, the reaction procedure is as follows: 1, preparation of 2-bromo-3-hydroxypyridine, and 2, preparation of 2-bromo-3- methoxypyridine; to be more specific, an aqueous solution of sodium hydroxide is cooled to -10 to 0 DEG C with an ice-salt bath in the temperature range, liquid bromine is added dropwise; 3- hydroxypyridine is dissolved in the aqueous solution of sodium hydroxide, then the aqueous solution of sodium hydroxide is added dropwise into the liquid bromine solution, the temperature of the system is maintained at 10-15 DEG C; after the dropwise addition, the system is stirred for 2.5-3 hours at room temperature, an acid is assed for adjusting pH to 7; the resulting crude product is recrystallized to obtain 2-bromo-3-hydroxypyridine. The beneficial effects comprise mild reaction conditions, short routes and high yield.
Description
Technical field
The invention belongs to technical field of organic synthesis, specifically the preparation method of the bromo-3-Methoxy Pyridine of a kind of 2-.
Background technology
Pyridine and its derivatives is distributed in nature widely.Many plant constituents are as all contained pyridine ring compound in the structure of alkaloid etc., they are the bases producing many important compound, are indispensable raw materials during medicine, agricultural chemicals, dyestuff, tensio-active agent, rubber ingredients, fodder additives, foodstuff additive, tackiness agent etc. are produced.
The existing method synthetic route preparing the bromo-3-Methoxy Pyridine of 2-is long, processing condition are harsh, yield is low, and aftertreatment bothers.
Summary of the invention
The object of the invention is to overcome in prior art the technical deficiency that operational path is long, reaction conditions is harsh, yield is low, the preparation method of the bromo-3-Methoxy Pyridine of 2-that a kind of route is short, mild condition, yield are high is provided.
For solving the problems of the technologies described above, the technical solution used in the present invention is as follows:
A preparation method for the bromo-3-Methoxy Pyridine of 2-, reactions steps is as follows:
(1) preparation of the bromo-3-pyridone of 2-: aqueous sodium hydroxide solution is cooled to-10-0 DEG C with cryosel bath, in this temperature range, drips bromine; Be dissolved in aqueous sodium hydroxide solution by 3-pyridone, then this solution is added drop-wise in above-mentioned bromine solution, maintenance system temperature is 10-15 DEG C; Drip, stirring at room temperature 2.5-3 hour, then be 7 with acid for adjusting pH; Gained crude product recrystallization, obtains the bromo-3-pyridone of 2-.
(2) preparation of the bromo-3-Methoxy Pyridine of 2-: joined by sodium in methyl alcohol, oil bath is warming up to backflow, keeps system backflow, joins in above-mentioned system by the DMF solution of bromo-for 2-3-pyridone; Stir 10-15 minute, underpressure distillation removes most methyl alcohol, adds methyl iodide, stirred overnight at room temperature in remaining mixture, underpressure distillation removing DMF, is cooled to room temperature, adds extracted with diethyl ether, layering again, and wash twice with saturated aqueous common salt, dry, distillation, obtains the bromo-3-Methoxy Pyridine of 2-.
Further, in described step (1), the massfraction of aqueous sodium hydroxide solution is 40%.
Further, the acid in described step (1) is the vitriol oil.
Further, in described step (1) recrystallization volume fraction be 75% ethanolic soln carry out.
Employing the invention has the beneficial effects as follows: reaction conditions is gentle, route is short, yield is high.
Embodiment
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1
(1) preparation of the bromo-3-pyridone of 2-: the aqueous sodium hydroxide solution of 60ml40% is cooled to-10-0 DEG C with cryosel bath, in this temperature range, drips bromine 16g(0.1mol); By 3-pyridone 9.8g(0.1mol) be dissolved in the aqueous sodium hydroxide solution of 50ml40%, then this solution is added drop-wise in above-mentioned bromine solution, keep system temperature to be 10 DEG C; Drip, stirring at room temperature 2.5 hours, then be 7 with acid for adjusting pH; Gained crude product recrystallization, obtain the bromo-3-pyridone of 2-, yield is 70%.
(2) preparation of the bromo-3-Methoxy Pyridine of 2-: be added in 20ml methyl alcohol by 0.7g sodium, oil bath is warming up to backflow, keeps system backflow, is dissolved in 50mlDMF by bromo-for 5g 2-3-pyridone, then is added drop-wise in the methanol solution of sodium; Stir 10 minutes, underpressure distillation removes most methyl alcohol, adds 1.9g methyl iodide in remaining mixture, stirred overnight at room temperature, then underpressure distillation removing DMF, be cooled to room temperature, 60ml ether divides three times and adds, extraction, layering, organic layer saturated aqueous common salt washes twice, with anhydrous sodium sulfate drying, distillation, obtain the bromo-3-Methoxy Pyridine of 2-, yield is 75%.
Embodiment 2
(1) preparation of the bromo-3-pyridone of 2-: the aqueous sodium hydroxide solution of 60ml40% is cooled to-10-0 DEG C with cryosel bath, in this temperature range, drips bromine 16g(0.1mol); By 3-pyridone 9.8g(0.1mol) be dissolved in the aqueous sodium hydroxide solution of 50ml40%, then this solution is added drop-wise in above-mentioned bromine solution, keep system temperature to be 15 DEG C; Drip, stirring at room temperature 3 hours, then be 7 with acid for adjusting pH; Gained crude product recrystallization, obtain the bromo-3-pyridone of 2-, yield is 75%.
(2) preparation of the bromo-3-Methoxy Pyridine of 2-: be added in 30ml methyl alcohol by 0.7g sodium, oil bath is warming up to backflow, keeps system backflow, is dissolved in 50mlDMF by bromo-for 5g 2-3-pyridone, then is added drop-wise in the methanol solution of sodium; Stir 15 minutes, underpressure distillation removes most methyl alcohol, adds 1.9g methyl iodide in remaining mixture, stirred overnight at room temperature, then underpressure distillation removing DMF, be cooled to room temperature, 60ml ether divides three times and adds, extraction, layering, organic layer saturated aqueous common salt washes twice, with anhydrous sodium sulfate drying, distillation, obtain the bromo-3-Methoxy Pyridine of 2-, yield is 80%.
This embodiment is preferred forms.
Embodiment 3
(1) preparation of the bromo-3-pyridone of 2-: the aqueous sodium hydroxide solution of 60ml40% is cooled to-10-0 DEG C with cryosel bath, in this temperature range, drips bromine 16g(0.1mol); By 3-pyridone 9.8g(0.1mol) be dissolved in the aqueous sodium hydroxide solution of 50ml40%, then this solution is added drop-wise in above-mentioned bromine solution, keep system temperature to be 10 DEG C; Drip, stirring at room temperature 3 hours, then be 7 with acid for adjusting pH; Gained crude product recrystallization, obtain the bromo-3-pyridone of 2-, yield is 70%.
(2) preparation of the bromo-3-Methoxy Pyridine of 2-: be added in 40ml methyl alcohol by 0.7g sodium, oil bath is warming up to backflow, keeps system backflow, is dissolved in 50mlDMF by bromo-for 5g 2-3-pyridone, then is added drop-wise in the methanol solution of sodium; Stir 15 minutes, underpressure distillation removes most methyl alcohol, adds 1.9g methyl iodide in remaining mixture, stirred overnight at room temperature, then underpressure distillation removing DMF, be cooled to room temperature, 60ml ether divides three times and adds, extraction, layering, organic layer saturated aqueous common salt washes twice, with anhydrous sodium sulfate drying, distillation, obtain the bromo-3-Methoxy Pyridine of 2-, yield is 75%.
Claims (4)
1. a preparation method for the bromo-3-Methoxy Pyridine of 2-, is characterized in that reactions steps is as follows:
(1) preparation of the bromo-3-pyridone of 2-: aqueous sodium hydroxide solution is cooled to-10-0 DEG C with cryosel bath, in this temperature range, drips bromine; Be dissolved in aqueous sodium hydroxide solution by 3-pyridone, then this solution is added drop-wise in above-mentioned bromine solution, maintenance system temperature is 10-15 DEG C; Drip, stirring at room temperature 2.5-3 hour, then be 7 with acid for adjusting pH; Gained crude product recrystallization, obtains the bromo-3-pyridone of 2-;
(2) preparation of the bromo-3-Methoxy Pyridine of 2-: be added to by sodium in methyl alcohol, oil bath is warming up to backflow, keeps system backflow, joins in above-mentioned system by the DMF solution of bromo-for 2-3-pyridone; Stir 10-15 minute, underpressure distillation removes most methyl alcohol, adds methyl iodide, stirred overnight at room temperature in remaining mixture, underpressure distillation removing DMF, is cooled to room temperature, adds extracted with diethyl ether, layering again, and wash twice with saturated aqueous common salt, dry, distillation, obtains the bromo-3-Methoxy Pyridine of 2-.
2. the preparation method of the bromo-3-Methoxy Pyridine of a kind of 2-according to claim 1, is characterized in that the massfraction of aqueous sodium hydroxide solution in described step (1) is 40%.
3. the preparation method of the bromo-3-Methoxy Pyridine of a kind of 2-according to claim 1, is characterized in that the acid in described step (1) is the vitriol oil.
4. the preparation method of the bromo-3-Methoxy Pyridine of a kind of 2-according to claim 1, it is characterized in that recrystallization volume fraction in described step (1) be 75% ethanolic soln carry out.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1282326A (en) * | 1997-12-19 | 2001-01-31 | 武田药品工业株式会社 | Anilide derivative, production and use thereof |
| CN1832944A (en) * | 2003-08-20 | 2006-09-13 | 伊莱利利公司 | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
-
2015
- 2015-07-24 CN CN201510438913.6A patent/CN105017136A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1282326A (en) * | 1997-12-19 | 2001-01-31 | 武田药品工业株式会社 | Anilide derivative, production and use thereof |
| CN1832944A (en) * | 2003-08-20 | 2006-09-13 | 伊莱利利公司 | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
Non-Patent Citations (2)
| Title |
|---|
| GARY J. CLARK AND LESLIE W. DEADY: "Synthetic Uses of the Sequential Ring Positional Reactivity in Pyridin-3-01 and Derivatives", 《AUST. J. CHEM.》 * |
| MARCELLO TIECCO等: "Total synthesis of Orellamine", 《TETRAHEDRON》 * |
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