CN104326944A - Method for preparing Boc-L-threonine - Google Patents
Method for preparing Boc-L-threonine Download PDFInfo
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- CN104326944A CN104326944A CN201410611006.2A CN201410611006A CN104326944A CN 104326944 A CN104326944 A CN 104326944A CN 201410611006 A CN201410611006 A CN 201410611006A CN 104326944 A CN104326944 A CN 104326944A
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- threonine
- boc
- potassium hydroxide
- method preparing
- crystallization
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Abstract
The invention provides a method for preparing Boc-L-threonine. The method comprises the following steps: mixing L-threonine with an aqueous solution of potassium hydroxide, adding (Boc)2O in batches, and controlling reaction conditions to obtain Boc-L-threonine with high yield. The method provided by the invention is low in cost, simple and convenient in method, safe to operate, small in pollution and high in yield, is easy to achieve industrial production, and provides a new method for industrially producing Boc-L-threonine.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to a kind of method preparing Boc-L-Threonine.
Background technology
Boc-L-Threonine is mainly used in Peptide systhesis, is mainly used in the application of multi-medicament and biotechnology.
Threonine is a kind of important nutrition-fortifying agent, can intensified cereal, cake, milk-product, and the same with tryptophane have relieving fatigue, the effect of enhancing development.Pharmaceutically, owing to containing hydroxyl in the structure of Threonine, to human body skin, there is water holding ability, be combined with oligonucleotide chain, Cell protection film is played an important role, can promote that phosphatide synthesizes and Fatty Acid Oxidation in vivo.Its preparation has the medicinal usefulness of promotion human development's anti-fatty liveranti-fatty liver, is a composition in aminoacids complex transfusion.Meanwhile, Threonine is again the microbiotic of the efficient low allergy of manufacture one class---the raw material of monobactam.
Threonine is used for the aspects such as medicine, chemical reagent, food fortifier, fodder additives.Particularly fodder additives aspect consumption increases fast, and it often adds in the feed of teenage piglet and poultry, is the second limiting amino acid of pig feed and the 3rd limiting amino acid of poultry feed.
In sum; Threonine tool has been widely used and acts on; and in prior art; the important intermediate raw material of multiple medicine and biotechnology to L-threonine protection as protecting group using Boc; and all there is certain defect and certain limitation in the method for the existing Boc-L-of preparation Threonine; make to produce inadequate Environmental Safety, yield is lower.
Summary of the invention
The present invention is intended to the limitation overcoming above-mentioned existing Boc-L-Threonine synthetic method, a kind of method preparing Boc-L-Threonine is provided, the present invention is by under aqueous solution condition wherein a kind of to L-threonine, sodium carbonate or sodium bicarbonate, adds (Boc) in batches
2o, by controlling reaction conditions, high yield obtains Boc-L-Threonine.Adopt the present invention, with low cost, method is easy, operational safety, and pollute little, productive rate is high, easily realizes suitability for industrialized production.For suitability for industrialized production Boc-L-Threonine provides a kind of new method.
For achieving the above object, the technical solution used in the present invention is as follows:
Prepare a method for Boc-L-Threonine, it is characterized in that step is as follows:
(1) L-threonine is mixed with potassium hydroxide solution;
(2) repeatedly add (Boc) in batches
2o reacts;
(3) acidity is adjusted to, reextraction;
(4) merge organic layer, be washed till neutrality, dry;
(5) crystallization is filtered, and obtains Boc-L-Threonine.
Further, mixed by L-threonine in described (1) with potassium hydroxide solution, concrete steps are dissolved in water to L-threonine for the potassium hydroxide adding 0.0005mol/L ~ 0.001mol/L, PH=9 ~ 11.
Further, be adjusted to acidic twice extraction in described (3), concrete steps, for adding hydrochloric acid soln, after being adjusted to acid PH=2 ~ 3, adding tert-butyl acetate and repeatedly extract.
Further, merge organic layer, be washed till neutrality in described (4), dry, adopt salt to be washed to neutral for good, time of drying controls at 8 ~ 12h.
Further, in described (5), crystallization is filtered, and concrete steps, for adding normal heptane crystallization and filtering, obtain Boc-L-Threonine.
Beneficial effect of the present invention is as follows:
The present invention is suitable for simple condition low cost production Boc-L-Threonine.The present invention adopts nontoxic non-hazardous (Boc)
2o as protection reagent, by changing alkaline condition, by controlling inventory and feed way one-step synthesis target compound.
Produce Boc-L-Threonine with method provided by the invention, yield reaches more than 90%, and comparatively previous methods improves a lot.The present invention produces product and easily to process and foreign matter content is extremely low, and Boc-L-Threonine purity can reach more than 94%.The present invention due to reaction conditions simple, use materials safety environmental protection, very friendly with personnel to production environment.
The present invention is with low cost, and method is easy, operational safety, and pollute little, productive rate is high, easily realizes suitability for industrialized production.For suitability for industrialized production Boc-L-Threonine provides a kind of new method.
Embodiment
The embodiment of form by the following examples, is described in further detail foregoing of the present invention again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example, all technology realized based on foregoing of the present invention all belong to scope of the present invention.
Embodiment one:
1., by 15.8gL-Threonine, add the 0.0005mol/L potassium bicarbonate solution stirring and dissolving of 200ml, then add (Boc) of 8g
2o reacts 2 hours, then adds (Boc) of 8g
2o reacts 2 hours, finally adds (Boc) of 9g
2o reacts 2 hours.
2. after regulating PH=3 with 0.001mol/L hydrochloric acid, then use tert-butyl acetate 0.4L/ time, extracted products three times.Merge ester layer, wash neutrality with salt.Add 15 grams of anhydrous sodium sulfate dryings 8 hours.
3. filter, filtrate reduced in volume is done, and adds the crystallization of 50ml petroleum ether and stirring.Centrifugal go out product, dry.Obtain product 22.4g.Productive rate 91.73%.
Embodiment two:
1., by 1.1kgL-Threonine, add the 0.0008mol/L potassium bicarbonate solution stirring and dissolving of 7L.Add again (Boc) of 433g
2o reacts 2 hours, then adds (Boc) of 433g
2o reacts 2 hours, finally adds (Boc) of 454g
2o reacts 3 hours.
2. after regulating PH=3 with 0.004mol/L hydrochloric acid, then use tert-butyl acetate 1L/ time, extracted products four times.Merge ester layer, wash neutrality with salt.Add 300 grams of anhydrous sodium sulfate dryings 10 hours.
3. filter, filtrate reduced in volume is done, and adds the crystallization of 2L petroleum ether and stirring.Leach product, dry.Obtain product 1672g.Productive rate 92.89%.
Claims (5)
1. prepare a method for Boc-L-Threonine, it is characterized in that step is as follows:
(1) L-threonine is mixed with potassium hydroxide solution;
(2) repeatedly add (Boc) in batches
2o reacts;
(3) acidity is adjusted to, reextraction;
(4) merge organic layer, be washed till neutrality, dry;
(5) crystallization is filtered, and obtains Boc-L-Threonine.
2. a kind of method preparing Boc-L-Threonine according to claim 1, it is characterized in that: in described (1), L-threonine is mixed with potassium hydroxide solution, concrete steps are dissolved in water to L-threonine for the potassium hydroxide adding 0.0005mol/L ~ 0.001mol/L, PH=9 ~ 11.
3. a kind of method preparing Boc-L-Threonine according to claim 1, is characterized in that: be adjusted to acidic twice extraction in described (3), concrete steps, for adding hydrochloric acid soln, after being adjusted to acid PH=2 ~ 3, adding tert-butyl acetate and repeatedly extract.
4. a kind of method preparing Boc-L-Threonine according to claim 1, is characterized in that: merge organic layer in described (4), be washed till neutrality, dry, and adopt salt to be washed to neutral for good, time of drying controls at 8 ~ 12h.
5. a kind of method preparing Boc-L-Threonine according to claim 1, is characterized in that: in described (5), crystallization is filtered, and concrete steps, for adding normal heptane crystallization and filtering, obtain Boc-L-Threonine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410611006.2A CN104326944A (en) | 2014-11-04 | 2014-11-04 | Method for preparing Boc-L-threonine |
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| CN201410611006.2A CN104326944A (en) | 2014-11-04 | 2014-11-04 | Method for preparing Boc-L-threonine |
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| CN104326944A true CN104326944A (en) | 2015-02-04 |
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| CN201410611006.2A Pending CN104326944A (en) | 2014-11-04 | 2014-11-04 | Method for preparing Boc-L-threonine |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999014238A1 (en) * | 1997-09-18 | 1999-03-25 | Hyundai Pharm. Ind. Co., Ltd. | Process for the preparation of calcitonin |
| CN1793110A (en) * | 2005-12-20 | 2006-06-28 | 武汉大学 | Process for preparing Boc protected amino acid by (Boc) O |
| CN1814585A (en) * | 2005-02-06 | 2006-08-09 | 扬州宝盛生物化工有限公司 | Method for synthesizing N-tert-butoxy-oxo-L-isoleucine |
| CN1974551A (en) * | 2006-12-15 | 2007-06-06 | 北京赛科药业有限责任公司 | Process of synthesizing (2S-trans)-3-methyl-4-oxo-1-azacyclo butyl sulfonic acid |
| CN101362713A (en) * | 2008-09-17 | 2009-02-11 | 重庆莱美药业股份有限公司 | Preparation method of (3S-trans)-3-amido-4-methyl-2-oxo-1-sulfoazetidine |
| WO2013024383A1 (en) * | 2011-08-12 | 2013-02-21 | Alembic Pharmaceuticals Limited | An improved process for the preparation of lacosamide |
| CN103274968A (en) * | 2013-06-04 | 2013-09-04 | 上海同昌生物医药科技有限公司 | Method for producing amantadine compound |
-
2014
- 2014-11-04 CN CN201410611006.2A patent/CN104326944A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999014238A1 (en) * | 1997-09-18 | 1999-03-25 | Hyundai Pharm. Ind. Co., Ltd. | Process for the preparation of calcitonin |
| CN1814585A (en) * | 2005-02-06 | 2006-08-09 | 扬州宝盛生物化工有限公司 | Method for synthesizing N-tert-butoxy-oxo-L-isoleucine |
| CN1793110A (en) * | 2005-12-20 | 2006-06-28 | 武汉大学 | Process for preparing Boc protected amino acid by (Boc) O |
| CN1974551A (en) * | 2006-12-15 | 2007-06-06 | 北京赛科药业有限责任公司 | Process of synthesizing (2S-trans)-3-methyl-4-oxo-1-azacyclo butyl sulfonic acid |
| CN101362713A (en) * | 2008-09-17 | 2009-02-11 | 重庆莱美药业股份有限公司 | Preparation method of (3S-trans)-3-amido-4-methyl-2-oxo-1-sulfoazetidine |
| WO2013024383A1 (en) * | 2011-08-12 | 2013-02-21 | Alembic Pharmaceuticals Limited | An improved process for the preparation of lacosamide |
| CN103274968A (en) * | 2013-06-04 | 2013-09-04 | 上海同昌生物医药科技有限公司 | Method for producing amantadine compound |
Non-Patent Citations (1)
| Title |
|---|
| PHILIP GARNER AND JUNG MIN PARK: "The Synthesis and Configurational Stability of Differentially Protected β-Hydroxy-α-amino Aldehydes", 《J. ORG. CHEM.》 * |
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Application publication date: 20150204 |