CN107868066B - A kind of preparation method of chaff propylhomoser and its salt - Google Patents
A kind of preparation method of chaff propylhomoser and its salt Download PDFInfo
- Publication number
- CN107868066B CN107868066B CN201710552985.2A CN201710552985A CN107868066B CN 107868066 B CN107868066 B CN 107868066B CN 201710552985 A CN201710552985 A CN 201710552985A CN 107868066 B CN107868066 B CN 107868066B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- salt
- preparation
- iii
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Seasonings (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of chaff propylhomoser and its preparation methods of salt, comprising: 1) reacts formula (V) compound with alcohol to obtain formula (VI) compound；2) formula (VI) compound is reacted to obtain formula (III) compound with 2- haloacetyl furans；3) formula (III) compound obtains chaff propylhomoser or its salt through sour water solution.Wherein, R C1‑6Alkyl, R1It is halogen for amino protecting group (such as tert-butoxycarbonyl Boc), X.Simply, conveniently, raw material is easy to get the method for the invention.
Description
Technical field
The present invention relates to the preparation method of compound, in particular to a kind of method for preparing chaff propylhomoser and its salt.
Background technique
Chaff propylhomoser (furosine also known as furans element, structure see below formula), chemical name relies for ε-N-2- furfuryl-L-
Propylhomoserin, molecular weight are 254.28 (g/mol).Chaff propylhomoser is widely present in field of food, such as high-temperature sterilization liquid milk, infant formula
Milk powder, cereal, honey and baked goods are the series products that Maillard reaction occurs with lactose under the high temperature conditions for lactoprotein
One of, it is to judge that most accurate and important index occurs for Mei Lade early reaction.
In milk processing and detection field, furosine level and heating strength and storage in different types of dairy produce finished product
It is related to deposit the factors such as time, in pasteurize milk, direct method ultrahigh-temperature instant sterilized milk, indirect method ultrahigh-temperature instant sterilized milk
(UHT), content in method batch-sterilized milk is kept to respectively may be about 0.2mg/L, 2.2mg/L, 26mg/L and 270mg/L.Therefore, in milk
Control of product quality link, chaff propylhomoser concentration are commonly used for judging whether contain reconstituted milk in sterilized milk, and judge liquid milk at
The superiority and inferiority of quality, in food processing, detection industry, the formation of chaff propylhomoser and content become measurement Protein in Food biology
The important indicator of the extent of damage and whole nutritive value, is of great significance.
Currently, chaff propylhomoser detects sterling used and standard items are bought from offshore company, price is very expensive.In order to meet
The wilderness demand of the industry of food quality inspection at present and scientific research field needs to develop a kind of simple, practical chaff propylhomoser chemical synthesis side
Method.
Summary of the invention
The object of the present invention is to provide the preparation methods of a kind of formula (I) compound and its salt.
A kind of preparation method of formula (I) compound and its salt, comprising:
Wherein, R C1-6Alkyl, R1It is halogen for amino protecting group (such as tert-butoxycarbonyl Boc), X；
1) formula (V) compound is reacted to obtain formula (VI) compound with alcohol；
2) formula (VI) compound is reacted to obtain formula (III) compound with 2- haloacetyl furans；
3) formula (III) compound obtains formula (I) compound or its salt through sour water solution.
According to the present invention, in the step 1), the alcohol is preferably n-butanol, tert-butyl alcohol etc.；The reaction is in DCC and 4-
It is reacted in the presence of dimethylamino naphthyridine.
According to the present invention, in the step 2), the method carries out under alkaline condition, such as sodium carbonate.
According to the present invention, in the step 3), the acid can be HCl, H2SO4Deng.
According to the present invention, the method for the step 3) includes: and formula (III) compound is carried out amine protection reaction to obtain formula
(II) compound, for example, formula (III) compound and boc- anhydride reaction are obtained formula (II) compound；Formula (II) is changed later
It closes object and obtains formula (I) compound or its salt through sour water solution；
Wherein, R C1-6Alkyl, R1For amino protecting group (such as tert-butoxycarbonyl Boc).
The present invention also provides the methods of another preparation formula (I) compound or its salt, comprising:
Wherein, R1It is halogen for amino protecting group (such as tert-butoxycarbonyl Boc), X；
I) formula (V) compound is reacted to obtain formula (III ') compound with 2- haloacetyl furans；
II) formula (III ') compound obtains formula (I) compound or its salt through sour water solution.
According to the present invention, the step I) in, the method carries out under alkaline condition, such as sodium carbonate.
According to the present invention, the step II) in, the acid can be HCl, H2SO4Deng.
According to the present invention, the step II) method may include: by formula (III ') compound carry out amine protection react
To formula (II ') compound, for example, formula (III ') compound and boc- anhydride reaction are obtained formula (II ') compound；Later, will
Formula (II ') compound obtains formula (I) compound or its salt through sour water solution；
Wherein, R1For amino protecting group (such as tert-butoxycarbonyl Boc).
Simply, conveniently, raw material is easy to get the method for the invention, and can obtain the chaff propylhomoser and its salt of high-purity.
Specific embodiment
Embodiment 1
Boc-L- lysine (1 equivalent) is dissolved in isobutanol, is added dicyclohexylcarbodiimide (DCC) (1.1 equivalent)
With the 4-dimethylaminopyridine (0.05 equivalent) of catalytic amount, reaction solution reacts for 24 hours at room temperature, and water and second are added into reaction solution
Acetoacetic ester, extraction, organic layer are washed with water three times, and anhydrous magnesium sulfate is dry, and solvent is removed under reduced pressure, obtains thick white object.Column color
Spectrum separation (eluant, eluent: petrol ether/ethyl acetate=1/1) obtains compound (A).
Compound (A) (1 equivalent) is dissolved in DMF, sodium carbonate is added, 2- bromoacetyl furans (1 equivalent) is dissolved in
DMF is simultaneously added dropwise in above-mentioned solution.Suitable quantity of water is added in fully reacting, and Boc acid anhydrides is added dropwise, is completely converted into compound (B)
After compound (C), methylene chloride extraction, liquid separation is added.Dry concentration, pillar layer separation (petroleum ether: ethyl acetate=2:1) are dense
Contracting obtains compound (C).
Compound (C) is dissolved in dioxane, the hydrogen chloride solution of dioxane is added dropwise, to completion of dropwise addition, stirring
Reaction, until compound (C) is completely converted into compound (I)；It filters later, filter cake is washed with ethyl acetate.
Embodiment 2
Boc-L- lysine (1 equivalent) is dissolved in DMF, sodium carbonate is added, 2- bromoacetyl furans (1 equivalent) is molten
Solution is in DMF and is added dropwise in above-mentioned solution.Suitable quantity of water is added in fully reacting, and Boc acid anhydrides is added dropwise, and all turns to compound (D)
Turn to compound (E).Methylene chloride extraction, liquid separation is added.Dry concentration, pillar layer separation (petroleum ether: ethyl acetate=5:1)
It is concentrated to get compound (E).
Compound (E) is dissolved in suitable dioxane, the hydrogen chloride solution of dioxane is added dropwise, wait which knot is added dropwise
Beam is stirred to react, until compound (E) is completely converted into compound (I)；It filters later, filter cake is washed with ethyl acetate.
Claims (9)
1. the preparation method of a kind of formula (I) compound and its salt, comprising:
Wherein, R C1-6Alkyl, R1For amino protecting group, X is halogen；
1) formula (V) compound is reacted to obtain formula (VI) compound with alcohol；
2) formula (VI) compound is reacted under alkaline condition to obtain formula (III) compound with 2- haloacetyl furans；
3) formula (III) compound obtains formula (I) compound or its salt through sour water solution；
The step 3) includes: that formula (III) compound is carried out amine protection reaction to obtain formula (II) compound, later, by formula
(II) compound obtains formula (I) compound or its salt through sour water solution；
Wherein, R C1-6Alkyl, R1For amino protecting group.
2. preparation method as described in claim 1, wherein in the step 1), the alcohol is n-butanol or the tert-butyl alcohol；It is described
Reaction is reacted in the presence of DCC and 4-dimethylaminopyridine.
3. preparation method as described in claim 1, wherein in the step 2), the alkaline condition is sodium carbonate.
4. preparation method as described in claim 1, wherein in the step 3), the acid is HCl or H2SO4。
5. preparation method as described in claim 1, wherein the step 3) includes: by formula (III) compound and Boc-acid
Anhydride reactant obtains formula (II) compound；Later, formula (II) compound is obtained into formula (I) compound or its salt through sour water solution.
6. preparation method as described in claim 1, wherein R1For tert-butoxycarbonyl Boc.
7. a kind of preparation method of formula (I) compound or its salt, comprising:
Wherein, R1For amino protecting group, X is halogen；
I) formula (V) compound is reacted under alkaline condition to obtain formula (III ') compound with 2- haloacetyl furans；
II) formula (III ') compound obtains formula (I) compound or its salt through sour water solution；
The step II) it include: that formula (III ') compound is carried out amine protection reaction to obtain formula (II ') compound；Later by formula
(II ') compound obtains chaff propylhomoser or its salt through sour water solution；
Wherein, R1For amino protecting group.
8. preparation method as claimed in claim 7, wherein the step II) in, the acid is HCl or H2SO4。
9. preparation method as claimed in claim 7, wherein the step II) it include: by formula (III ') compound and Boc-
Anhydride reaction obtains formula (II ') compound；Formula (II ') compound is obtained into chaff propylhomoser or its salt through sour water solution later.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710552985.2A CN107868066B (en) | 2017-07-07 | 2017-07-07 | A kind of preparation method of chaff propylhomoser and its salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710552985.2A CN107868066B (en) | 2017-07-07 | 2017-07-07 | A kind of preparation method of chaff propylhomoser and its salt |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107868066A CN107868066A (en) | 2018-04-03 |
| CN107868066B true CN107868066B (en) | 2019-11-12 |
Family
ID=61761799
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710552985.2A Active CN107868066B (en) | 2017-07-07 | 2017-07-07 | A kind of preparation method of chaff propylhomoser and its salt |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107868066B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109307761B (en) * | 2018-10-09 | 2021-06-15 | 华南农业大学 | Indirect competitive ELISA method for detecting furaldehyde |
| CN114853698A (en) * | 2022-06-08 | 2022-08-05 | 深圳振强生物技术有限公司 | Preparation method of furosine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104610079A (en) * | 2014-10-13 | 2015-05-13 | 湖州海创生物科技有限公司 | Salbutamol hapten derivative, and artificial salbutamol antigen and preparation method and application thereof |
-
2017
- 2017-07-07 CN CN201710552985.2A patent/CN107868066B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104610079A (en) * | 2014-10-13 | 2015-05-13 | 湖州海创生物科技有限公司 | Salbutamol hapten derivative, and artificial salbutamol antigen and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 2-呋喃甲酰基甲基丙氨酸的合成;杨亚军等;《化学试剂》;20110430;第33卷(第4期);第297-298页 * |
| Marı＇a Luz Sanz et al..Formation of Amadori Compounds in Dehydrated Fruits.《J. Agric. Food Chem.》.2001,第49卷第5228-5231页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107868066A (en) | 2018-04-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107868066B (en) | A kind of preparation method of chaff propylhomoser and its salt | |
| US20160318998A1 (en) | Aflatoxin nanobody immunoabsorbent and immunoaffinity column and preparation method and use thereof | |
| CN104230924B (en) | A kind of synthetic method of moxifloxacin hydrochloride | |
| CN106316993B (en) | A kind of dinotefuran synthetic method | |
| CN104945383B (en) | Hold in the palm his preparation method of pyrrole department | |
| CN109265401A (en) | A kind of preparation method and application of iprodione haptens and antigen | |
| CN106117148A (en) | A kind of preparation and purification technique of Lopinavir | |
| CN107022023A (en) | A kind of synthetic method of 6 benzyl aminoadenine artificial antigen | |
| CN105849106B (en) | Key intermediate and impurity in Eliquis synthesis：Eliquis diol ester | |
| CN106146419A (en) | Xanthine oxidase inhibitor | |
| CN113698394A (en) | Propiconazole hapten as well as preparation method and application thereof | |
| CN101643477B (en) | Synthesis method of cefradine | |
| CN106674040B (en) | A kind of method that solvent-free catalysis-free agent prepares N- aryl amides | |
| US10100055B2 (en) | Imidazopyrroloquinoline salt, method for producing the same, medicament, cosmetic, and food | |
| CN110938007B (en) | Dicofol hapten, artificial antigen, antibody, synthetic method and application thereof | |
| KR20190022560A (en) | Pyrroloquinoline quinone monosodium, a method for preparing the same, and a composition comprising the same | |
| CN105622430A (en) | Preparation method of ethanediamine dihydroiodide | |
| Goto et al. | Formation of a stable sulfenic acid by hydrolysis of a thionitrate and a sulfenyl bromide | |
| CN102079728B (en) | Tripolycyanamide analogue, preparation method of tripolycyanamide analogue and intermediate used in preparation method | |
| CN102557903B (en) | Preparation method of 4-hydroxyl-2-methoxybenzaldehyde | |
| CN108822113A (en) | A kind of synthetic method of 1H- pyrazolo [3,4-d] pyrimidine -4- alcohol | |
| CN110357775A (en) | A kind of preparation method and preparation facilities of phthalic acid | |
| CN112341353B (en) | Propyl betaine and preparation method thereof | |
| CN113817045B (en) | Method for synthesizing clopidol artificial antigen and application of clopidol artificial antigen in colloidal gold kit | |
| CN106478620A (en) | A kind of preparation method of pioglitazone impurity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |