CN103880739A - Synthetic method for 2-BOC-amino-3-hydroxypyridine - Google Patents
Synthetic method for 2-BOC-amino-3-hydroxypyridine Download PDFInfo
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- CN103880739A CN103880739A CN201410089095.9A CN201410089095A CN103880739A CN 103880739 A CN103880739 A CN 103880739A CN 201410089095 A CN201410089095 A CN 201410089095A CN 103880739 A CN103880739 A CN 103880739A
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- amino
- boc
- pyridone
- synthetic method
- hydroxypyridine
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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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method for 2-BOC-amino-3-hydroxypyridine. The synthetic method for 2-BOC-amino-3-hydroxypyridine comprises the following steps: by taking 2-amino-3-hydroxypyridine and di-tert-butyl dicarbonate as raw materials, reacting for 2-24 hours in an organic solvent at minus 10DEG C-50DEG C in the presence of base, and purifying to obtain 2-BOC-amino-3-hydroxypyridine. The synthetic method for preparing 2-BOC-amino-3-hydroxypyridine is mild in reaction conditions, has no special requirements for reaction equipment, and is simple for after-treatment and easy to operate and popularize; meanwhile, a product is stable in quality and high in purity.
Description
Technical field
The invention belongs to organic synthesis field, particularly a kind of synthetic method of 2-BOC-amino-3-pyridone.
Background technology
2-amino-3-pyridone is an important organic synthesis intermediate, the particularly research in pharmaceutical chemistry and application.Its more function group or potential more function group are its key points that is used to organic synthesis.But 2-amino-3-pyridone molecule will prevent from mutually combining between amino, therefore, when synthetic, some amino or carboxy protective must be got up, so that reaction can be undertaken by desired mode
BOC, i.e. BOC acid anhydrides, another name tert-Butyl dicarbonate, DIBOC.BOC is transparent crystallization or liquid, in organic synthesis, be used for introducing tertbutyloxycarbonyl protecting group because of.Apply to especially amino acid whose amido protecting, be widely used in medicine, protein and polypeptide are synthetic, and biological chemistry food, in the multiple products such as makeup synthetic.BOC is introduced to 2-amino-3-pyridone, synthesize 2-BOC-amino-3-pyridone, can greatly improve the stability of pharmaceutical intermediate.Therefore, develop a kind of raw material cheap and easy to get, easy and simple to handle, reaction conditions gentleness, production cost is low, and productive rate is high, is applicable to scale operation, and the method for storage, production process safety is completely necessary.
Summary of the invention
The present invention is in order to make up the defect of prior art, and a kind of synthetic method that can be applied to laboratory and the synthetic 2-BOC-amino-3-pyridone of industrialization is provided.
The present invention is achieved through the following technical solutions:
A synthetic method for 2-BOC-amino-3-pyridone, is characterized in that, comprises the following steps:
Take 2-amino-3-pyridone and tert-Butyl dicarbonate as raw material, in organic solvent, at 0 ~ 100 ℃ of temperature, react and within 0 ~ 24 hour, generate 2-BOC-amino-3-pyridone, after purifying, obtain 2-BOC-amino-3-pyridone sterling.
Described organic solvent is the trimethyl carbinol and ethanol, methyl alcohol, ethyl acetate, propyl alcohol, one or both in Virahol.
Described raw material consumption is: 2-amino-3-pyridone: tert-Butyl dicarbonate=1:0.5 ~ 5.5 are more than mol ratio.
Described solvent load is: 2-amino-3-pyridone: solvent=1:1 ~ 4.5 are more than weight ratio.
Described purification step is followed successively by evaporation concentration, recrystallization.
The solvent of described recrystallization is ethyl acetate, ethanol, methylene dichloride, one or both materials in normal hexane.
The invention has the beneficial effects as follows: adopt the present invention to prepare 2-BOC-amino-3-pyridone, reaction conditions gentleness, does not have particular requirement to conversion unit, and aftertreatment is simple, easy handling, is easy to promote, constant product quality simultaneously, and purity is high.
embodiment
Embodiment 1:
In the round bottom single port flask of a 100ml, add the 45ml that mixes of the trimethyl carbinol and Virahol, insert thermometer and start magnetic stirring apparatus, and add 2-amino-3-pyridone of 11.0g, add tert-Butyl dicarbonate 67.5g, under 15 ℃ of stirrings, react 4 hours.TLC and GC are definite to have reacted.Revolve to steam and remove extraction agent, obtain thick product, obtain straight product 2-Boc amino-3-pyridone with ethyl acetate and normal hexane recrystallization, after being dried, calculated yield 66%, purity 97.32%.Nuclear magnetic resonance spectroscopy: 1HNMR (DMSO-d6) 400MHz: δ 8.658PPM(S, 1H); δ 8.252 (d, J=2.0Hz, 1H); δ 8.055 (d, J=2.0,1H); δ 7.303(S, 1H); δ 5.305(S, 2H).
Embodiment 2:
In the round bottom single port flask of a 2L, add the mixed solvent 600ml of the trimethyl carbinol and Virahol, insert thermometer and start magnetic stirring apparatus, and add 2-amino-3-pyridone of 187.5g, and add tert-Butyl dicarbonate 218.25g, under 50 ℃ of stirrings, react 3 hours.TLC and GC are definite to have reacted.Revolve to steam and remove extraction agent, obtain thick product, obtain straight product 2-Boc amino-3-pyridone with ethyl acetate and normal hexane recrystallization, after being dried, calculated yield 70%, purity 98.50%.Nuclear magnetic resonance spectroscopy: 1HNMR (DMSO-d6) 400MHz: δ 8.658PPM(S, 1H); δ 8.252 (d, J=2.0Hz, 1H); δ 8.055 (d, J=2.0,1H); δ 7.303(S, 1H); δ 5.305(S, 2H).
Embodiment 3:
In the flask with three necks,round bottom of a 10L, add methylene dichloride 6000ml, insert thermometer and condensation reflux unit is installed, and adding 2-amino-3-pyridone of 2333.4g, adding tert-Butyl dicarbonate 3703.5g, start magnetic stirring apparatus, 75 ℃ of stirring reactions 4 hours.TLC and GC are definite to have reacted.Revolve to steam and remove extraction agent, obtain thick product, obtain straight product 2-Boc amino-3-pyridone with ethyl acetate and normal hexane recrystallization, after being dried, calculated yield 73.5%, purity 98.30%.Nuclear magnetic resonance spectroscopy: 1HNMR (DMSO-d6) 400MHz: δ 8.658PPM(S, 1H); δ 8.252 (d, J=2.0Hz, 1H); δ 8.055 (d, J=2.0,1H); δ 7.303(S, 1H); δ 5.305(S, 2H).
Embodiment 4:
In the flask with three necks,round bottom of a 50L, add the mixed solvent 13L of the trimethyl carbinol and Virahol, insert thermometer and start magnetic stirring apparatus, and add 2-amino-3-pyridone of 4334g, and add tert-Butyl dicarbonate 8598 g, under 65 ℃ of stirrings, react 3 hours.TLC and GC are definite to have reacted.Revolve steam remove extraction agent, obtain thick product, with ethyl acetate and normal hexane recrystallization obtain straight product 2-Boc amino-3-pyridone be dried after, calculated yield 78%, purity 99.62%.Nuclear magnetic resonance spectroscopy: 1HNMR (DMSO-d6) 400MHz: δ 8.658PPM(S, 1H); δ 8.252 (d, J=2.0Hz, 1H); δ 8.055 (d, J=2.0,1H); δ 7.303(S, 1H); δ 5.305(S, 2H).
Claims (6)
1. a synthetic method for 2-BOC-amino-3-pyridone, is characterized in that, comprises the following steps:
Take 2-amino-3-pyridone and tert-Butyl dicarbonate as raw material, in organic solvent, at 0 ~ 100 ℃ of temperature, react and within 0 ~ 24 hour, generate 2-BOC-amino-3-pyridone, after purifying, obtain 2-BOC-amino-3-pyridone sterling.
2. the synthetic method of 2-BOC-amino-3-pyridone according to claim 1, is characterized in that: described organic solvent is the trimethyl carbinol and ethanol, methyl alcohol, ethyl acetate, propyl alcohol, one or both in Virahol.
3. the synthetic method of 2-BOC-amino-3-pyridone according to claim 1, is characterized in that: described raw material consumption is: 2-amino-3-pyridone: tert-Butyl dicarbonate=1:0.5 ~ 5.5 are more than mol ratio.
4. the synthetic method of 2-BOC-amino-3-pyridone according to claim 1, is characterized in that: described solvent load is: 2-amino-3-pyridone: solvent=1:1 ~ 4.5 are more than weight ratio.
5. the synthetic method of 2-BOC-amino-3-pyridone according to claim 1, is characterized in that: described purification step is followed successively by evaporation concentration, recrystallization.
6. the synthetic method of 2-BOC-amino-3-pyridone according to claim 5, is characterized in that: the solvent of described recrystallization is ethyl acetate ethanol, methylene dichloride, one or both materials in normal hexane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410089095.9A CN103880739A (en) | 2014-03-12 | 2014-03-12 | Synthetic method for 2-BOC-amino-3-hydroxypyridine |
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| CN201410089095.9A CN103880739A (en) | 2014-03-12 | 2014-03-12 | Synthetic method for 2-BOC-amino-3-hydroxypyridine |
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| CN201410089095.9A Pending CN103880739A (en) | 2014-03-12 | 2014-03-12 | Synthetic method for 2-BOC-amino-3-hydroxypyridine |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998015278A1 (en) * | 1996-10-07 | 1998-04-16 | Smithkline Beecham Corporation | Method for stimulating bone formation |
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2014
- 2014-03-12 CN CN201410089095.9A patent/CN103880739A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998015278A1 (en) * | 1996-10-07 | 1998-04-16 | Smithkline Beecham Corporation | Method for stimulating bone formation |
Non-Patent Citations (3)
| Title |
|---|
| FATEMEH JAHANI，ET AL.: "An efficient and highly chemoselective N-Boc protection of amines, amino acids, and peptides under heterogeneous conditions", 《MONATSH CHEM》 * |
| FATEMEH JAHANI,ET AL.: "Guanidine hydrochloride as an organocatalyst forN-Boc protection of amino groups", 《TETRAHEDRON LETTERS》 * |
| 赵颖俊等: "2-氨基-3-羟基吡啶的合成", 《广东化工》 * |
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Application publication date: 20140625 |