CN104326943A - Method for preparing Boc-L-serine - Google Patents
Method for preparing Boc-L-serine Download PDFInfo
- Publication number
- CN104326943A CN104326943A CN201410611008.1A CN201410611008A CN104326943A CN 104326943 A CN104326943 A CN 104326943A CN 201410611008 A CN201410611008 A CN 201410611008A CN 104326943 A CN104326943 A CN 104326943A
- Authority
- CN
- China
- Prior art keywords
- serine
- boc
- method preparing
- concrete steps
- crystallization
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for preparing Boc-L-serine. The method comprises the following steps: mixing L-serine with an aqueous solution of one of sodium carbonate and sodium hydrogen carbonate, adding (Boc)2O in batches, and controlling reaction conditions to obtain Boc-L-serine with high yield. The method provided by the invention is low in cost, simple and convenient in method, safe to operate, little in pollution and high in yield, is easy to achieve industrial production, and can provide a new method for industrially producing Boc-L-serine.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to a kind of method of synthesizing Boc-L-Serine.
Background technology
Boc-L-Serine is mainly used in Peptide systhesis, is mainly used in the application of multi-medicament and biotechnology.
Serine is a kind of non-essential amino acid, and it plays and acts in fat and the metabolism of lipid acid and the growth of muscle, because it contributes to the generation of immunoglobulin and antibody, the immunity system maintaining health also needs Serine.Serine all to play and acts in the synthesis of the sheath of the manufacture processing of cytolemma, muscle tissue and encirclement neurocyte.
Serine is widely used in configuration third generation Hausmam Amin 20 and accessory substance, and for the synthesis of multiple silk amino acid derivative, as cardiovascular, anticancer, acquired immune deficiency syndrome (AIDS) new drug and genetically engineered protected amino acid etc.; Serine can be applied to sports beverages, amino acid weight-reducing drinks etc.; Serine is used for animal-feed, can promote animal growth.
In sum; Serine tool has been widely used and acts on; and in prior art; the important intermediate raw material of multiple medicine and biotechnology to Serine 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 Serine; 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-Serine synthetic method, a kind of method preparing Boc-L-Serine is provided, the present invention is by under aqueous solution condition wherein a kind of to Serine, sodium carbonate or sodium bicarbonate, adds (Boc) in batches
2o, by controlling reaction conditions, high yield obtains Boc-L-Serine.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-Serine 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-Serine, it is characterized in that step is as follows:
(1) Serine is mixed with sodium carbonate or sodium hydrogen carbonate solution;
(2) repeatedly add (Boc) in batches
2o reacts;
(3) impurity is removed in extraction;
(4) acidity is adjusted to, reextraction;
(5) merge organic layer, be washed till neutrality, dry;
(6) crystallization is filtered, and obtains Boc-L-Serine.
Further, mixed by Serine in described (1) with sodium carbonate or sodium hydrogen carbonate solution, concrete steps are dissolved in water to Serine for the sodium carbonate or sodium bicarbonate adding 0.005mol/L ~ 0.010mol/L, PH=10 ~ 12.
Further, in described (3), impurity is removed in extraction, and concrete steps, for adding sherwood oil repeatedly extracting impurities, remove the organic layer comprising impurity.
Further, be adjusted to acidic twice extraction in described (4), concrete steps, for adding hydrochloric acid soln, after being adjusted to acid PH=1 ~ 3, adding tetrahydrofuran (THF) and repeatedly extract.
Further, merge organic layer, be washed till neutrality in described (5), dry, adopt salt to be washed to neutral for good, time of drying controls at 8 ~ 12h.
Further, in described (6), crystallization is filtered, and concrete steps, for adding sherwood oil crystallization and filtering, obtain Boc-L-Serine.
Beneficial effect of the present invention is as follows:
The present invention is suitable for simple condition low cost production Boc-L-Serine.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-Serine 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-Serine purity can reach more than 99%.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-Serine 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 18.1gL-Serine, add the 0.010mol/L sodium carbonate solution stirring and dissolving of 200ml, then add (Boc) of 8g
2o reacts 3 hours, then adds (Boc) of 8g
2o reacts 5 hours, finally adds (Boc) of 9g
2o reacts 7 hours.
2. use sherwood oil 10ml/ time, extracting impurities three times.After 3mol/L hydrochloric acid regulates PH=3, then use tetrahydrofuran (THF) 0.5L/ 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 23.1g.Productive rate 90.15%.
Embodiment two:
1., by 1kgL-Serine, add the 0.008mol/L sodium hydrogen carbonate solution stirring and dissolving of 7L.Add again (Boc) of 442g
2o reacts 4 hours, then adds (Boc) of 442g
2o reacts 7 hours, finally adds (Boc) of 497g
2o reacts 10 hours.
2. use sherwood oil 500ml/ time, extracting impurities four times.After 6mol/L hydrochloric acid regulates PH=3, then use tetrahydrofuran (THF) 1L/ time, extracted products four times.Merge ester layer, wash neutrality with salt.Add 300 grams of anhydrous sodium sulfate dryings 12 hours.
3. filter, filtrate reduced in volume is done, and adds the crystallization of 2L petroleum ether and stirring.Leach product, dry.Obtain product 1732g.Productive rate 95.79%.
Claims (6)
1. prepare a method for Boc-L-Serine, it is characterized in that step is as follows:
(1) Serine is mixed with sodium carbonate or sodium hydrogen carbonate solution;
(2) repeatedly add (Boc) in batches
2o reacts;
(3) impurity is removed in extraction;
(4) acidity is adjusted to, reextraction;
(5) merge organic layer, be washed till neutrality, dry;
(6) crystallization is filtered, and obtains Boc-L-Serine.
2. a kind of method preparing Boc-L-Serine according to claim 1, it is characterized in that: in described (1), Serine is mixed with sodium carbonate or sodium hydrogen carbonate solution, concrete steps are dissolved in water to Serine for the sodium carbonate or sodium bicarbonate adding 0.005mol/L ~ 0.010mol/L, PH=10 ~ 12.
3. a kind of method preparing Boc-L-Serine according to claim 1, is characterized in that: in described (3), impurity is removed in extraction, and concrete steps, for adding sherwood oil repeatedly extracting impurities, remove the organic layer comprising impurity.
4. a kind of method preparing Boc-L-Serine according to claim 1, is characterized in that: be adjusted to acidic twice extraction in described (4), concrete steps, for adding hydrochloric acid soln, after being adjusted to acid PH=1 ~ 3, adding tetrahydrofuran (THF) and repeatedly extract.
5. a kind of method preparing Boc-L-Serine according to claim 1, is characterized in that: merge organic layer in described (5), be washed till neutrality, dry, and adopt salt to be washed to neutral for good, time of drying controls at 8 ~ 12h.
6. a kind of method preparing Boc-L-Serine according to claim 1, is characterized in that: in described (6), crystallization is filtered, and concrete steps, for adding sherwood oil crystallization and filtering, obtain Boc-L-Serine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410611008.1A CN104326943A (en) | 2014-11-04 | 2014-11-04 | Method for preparing Boc-L-serine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410611008.1A CN104326943A (en) | 2014-11-04 | 2014-11-04 | Method for preparing Boc-L-serine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104326943A true CN104326943A (en) | 2015-02-04 |
Family
ID=52401769
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410611008.1A Pending CN104326943A (en) | 2014-11-04 | 2014-11-04 | Method for preparing Boc-L-serine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104326943A (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1681936A (en) * | 2002-09-09 | 2005-10-12 | 日本化药株式会社 | Process for producing optically active erythro 3-cyclohexylserines |
| 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 |
| CN101597288A (en) * | 2008-06-02 | 2009-12-09 | 北京大学 | 2-aminoacyl-β-Ka Lin-3-formyl tryptophan benzyl ester and its production and application |
| EP2487152A1 (en) * | 2010-11-17 | 2012-08-15 | UCB Pharma GmbH | Process for the preparation of Lacosamide including resolution of O-methyl-DL-serine |
| WO2013072936A2 (en) * | 2011-11-10 | 2013-05-23 | Ramamohan Rao Davuluri | A novel process for the preparation of (r)-n-benzyl-2 acetamido-3-methoxypropionamide |
| WO2014120786A1 (en) * | 2013-01-29 | 2014-08-07 | Naurex, Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
-
2014
- 2014-11-04 CN CN201410611008.1A patent/CN104326943A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1681936A (en) * | 2002-09-09 | 2005-10-12 | 日本化药株式会社 | Process for producing optically active erythro 3-cyclohexylserines |
| 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 |
| CN101597288A (en) * | 2008-06-02 | 2009-12-09 | 北京大学 | 2-aminoacyl-β-Ka Lin-3-formyl tryptophan benzyl ester and its production and application |
| EP2487152A1 (en) * | 2010-11-17 | 2012-08-15 | UCB Pharma GmbH | Process for the preparation of Lacosamide including resolution of O-methyl-DL-serine |
| WO2013072936A2 (en) * | 2011-11-10 | 2013-05-23 | Ramamohan Rao Davuluri | A novel process for the preparation of (r)-n-benzyl-2 acetamido-3-methoxypropionamide |
| WO2014120786A1 (en) * | 2013-01-29 | 2014-08-07 | Naurex, Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| PHILIP GARNER ，JUNG MIN PARK: "The Synthesis and Configurational Stability of Differentially Protected P-Hydroxy-a-amino Aldehydes", 《J. ORG. CHEM.》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101434608B (en) | Preparation of high-purity ellagic acid | |
| CN102268037B (en) | Process for purifying glufosinate-ammonium | |
| CN102040606A (en) | Synthetic method of vinpocetine | |
| CN108047029A (en) | A kind of preparation method of the extraction purification hydroxycitric acid from Garcinia Cambogia | |
| CN101307002A (en) | Recovery method of triethylamine in glyphosate mother liquid | |
| CN102887885B (en) | Preparation method of esomeprazole sodium | |
| CN109593092A (en) | A method of ellagic acid is synthesized using gallic acid-derivate | |
| CN104592081B (en) | A kind of synthetic method of aztreonam main ring | |
| CN101768165B (en) | Ellagic acid preparation method employing tara powder | |
| CN101585770A (en) | Caffeic acid diester compounds and prepartion method thereof, and application of preparing medicine for curing thrombus | |
| CN104326943A (en) | Method for preparing Boc-L-serine | |
| CN101270063A (en) | Method for preparing high purity solid cyanoacetic acid | |
| CN103664779A (en) | Preparation method of pefloxacin mesylate | |
| CN104478974B (en) | A kind of 20, the synthetic method of 23-dipiperidino-5-O-mycamino syl-tylono lide | |
| CN102617461A (en) | Novel method for refining aripiprazole | |
| CN104326960A (en) | Method for preparing Boc-L-proline | |
| CN104276964A (en) | Preparation method of Boc-glycine | |
| CN102093254B (en) | Preparation method of 3-(2,2,2-trimethylhydrazine)propionate dihydrate | |
| CN114044783B (en) | Preparation method of idosiban and intermediate thereof | |
| CN107686439A (en) | A kind of preparation method of the key intermediate of ALK inhibitor | |
| CN102964214B (en) | Method for preparing high-purity solanesol by using crude cigarette paste | |
| CN102382070A (en) | Method for preparing N',N'',N''',N''''-tetrabenzylcyclen compound | |
| CN102461974A (en) | Method for preparing food antioxidant from vinasse | |
| CN102731399B (en) | Preparation method of high-purity 3-methoxy-9 alpha, 13 alpha, 14 alpha morphinan hydrochloride | |
| CN102863423B (en) | Method for preparing isoquinolyl substituted pyrimidine derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150204 |