CN109369432A - (S) preparation method of the chloro- 2-amino-butyric acid ester of -4- - Google Patents
(S) preparation method of the chloro- 2-amino-butyric acid ester of -4- Download PDFInfo
- Publication number
- CN109369432A CN109369432A CN201811302666.7A CN201811302666A CN109369432A CN 109369432 A CN109369432 A CN 109369432A CN 201811302666 A CN201811302666 A CN 201811302666A CN 109369432 A CN109369432 A CN 109369432A
- Authority
- CN
- China
- Prior art keywords
- amino
- chloro
- butyric acid
- preparation
- acid ester
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
The present invention relates to field of agricultural herbicide, for the lower problem of yield, provide the preparation method of one kind chloro- 2-amino-butyric acid ester of (S) -4-, the technical solution is as follows: (S) -2- amino butyrolactone obtains corresponding S- homoserine ester by ring opening alcoholysis under acid catalysis, then target product is obtained by the chlorination of chlorinating agent, reaction equation is as follows:
Description
Technical field
The present invention relates to field of agricultural herbicide, more particularly, to the preparation side of one kind chloro- 2-amino-butyric acid ester of (S) -4-
Method.
Background technique
Typically, in field of agricultural herbicide, the different isomer of amino acid has different bioactivity, more
Situation is that only a kind of amino acid of chiral isomer has bioactivity for effective body, and another chiral isomer does not have then
Bioactivity or activity are very weak.
Glufosinate-ammonium is the amino acids steriland herbicide of German Hirst company exploitation, in the world extensively
Using.The L-glufosinate-ammonium that Japanese Mingzhi Fruit company develops accordingly is single L- chiral isomer, and experiments verify that, grass
The D body of ammonium phosphine is not no bioactivity, and L body bioactivity is 2 times of raceme.
For a long time being prepared by the production technology of L-glufosinate-ammonium, many enterprises are carrying on technical development always in field,
It is split including biological enzyme synthesis, biological enzyme and isomers conversion, chiral catalysis synthesis, chemical resolution and isomers turns
Change etc., and have numerous patents report, but the method for biological enzyme does not have report or the practice of any industrialization so far.Mingzhi Fruit
The chiral chemistry catalyst synthesis L-GAP of company's exploitation realizes industrialization in China, but its manufacturing cost is still not
Enough ideals.
Reporting one kind in patent US5442088 disclosed in German Hirst companies in 1994 with S-2- amino butyrolactone is
The chloro- 2-amino-butyric acid ester of (S) -4- of the method for Material synthesis L-glufosinate-ammonium, amido protecting is one of its core intermediate, is closed
Key intermediate process route is as follows:
Amido protecting wherein is passed through for chiral 2- amino butyrolactone.
Although this synthetic route can prepare the chloro- 2-amino-butyric acid ester of (S) -4-, needed in the reaction process of chlorination
Keep using excessive hydrogen chloride gas otherwise can not fully reacting, want the moisture of stringent limited reactions system otherwise open loop but
The by-product of no esterification will increase or even become major product so that when HCl proportion reduces raw material can not fully reacting, but HCl mistake
More side reactions for having amino to be deprotected again generate, so that the yield of the chloro- 2-amino-butyric acid ester of (S) -4- is lower, therefore also
Improve space.
Summary of the invention
In view of the deficiencies of the prior art, the present invention intends to provide one kind chloro- 2-amino-butyric acid ester of (S) -4-
Preparation method, have the advantages that yield is higher.
To achieve the above object, the present invention provides the following technical scheme that
The preparation method of one kind chloro- 2-amino-butyric acid ester of (S) -4-, (S) -2- amino butyrolactone is by opening under acid catalysis
Cyclic alcohol solution obtains corresponding S- homoserine ester, then obtains target product by the chlorination of chlorinating agent, reaction equation is as follows:
By using above-mentioned technical proposal, allow butyrolactone structure under strong acid catalyst, is realized in the system of alcohol
Synchronous open loop is synchronous to be esterified, and therefore constantly promotes chemical balance forward direction mobile, and high yield obtains (S) -4- hydroxyl -2- amino
Butyrate；Esterification by ring opening is directly catalyzed for substituted butyrolactone, the hydroxyl group contained by intermediate after esterification by ring opening
It is easier to be chlorinated and obtains the chloro- 2-amino-butyric acid ester of (S) -4- in high yield；And the chloro- 2-amino-butyric acid ester of (S) -4- can be very
(S) -4- chloro- 2- (methoxycarbonyl group imino group) methyl butyrate is readily obtained with the conjunction for L-glufosinate-ammonium by amido protecting
At.
The present invention is further arranged to: R is one of the alkyl of C1-C4 in the reaction equation.
By using above-mentioned technical proposal, since the carbochain of alcohol is shorter, the activity for carrying out ring opening alcoholysis reaction is higher, is easier to
In promoting chemical balance forward direction mobile, so that (S) -4- hydroxyl -2-amino-butyric acid ester yield is higher.
The present invention is further arranged to: R is methyl or ethyl in the reaction equation.
By using above-mentioned technical proposal, the carbochain using methanol or ethyl alcohol is shorter, allows to carry out ring opening alcoholysis reaction
Activity is higher, is easy to promote chemical balance forward direction mobile, so that (S) -4- hydroxyl -2-amino-butyric acid ester yield is higher.
The present invention is further arranged to: R is ethyl in the reaction equation.
It by using above-mentioned technical proposal, may make that reactivity is higher using ethyl alcohol, reduce by-product, promote chemistry flat
Weighing apparatus is positive mobile, so that (S) -4- hydroxyl -2-amino-butyric acid ester yield is higher.
The present invention is further arranged to: the catalyst is inorganic sulfonic acid or organic sulfonic acid.
By using above-mentioned technical proposal, so that the acidity of catalyst is stronger, so that the better effect of catalysis open loop, is improved
Reaction rate and reactivity.
The present invention is further arranged to: the catalyst is the concentrated sulfuric acid, benzene sulfonic acid, p-methyl benzenesulfonic acid, methane sulfonic acid, ethyl
Sulfonic acid.
By using above-mentioned technical proposal, so that the acidity of catalyst is stronger, so that the better effect of catalysis open loop, is improved
Reaction rate and reactivity.
The present invention is further arranged to: the catalyst is sulfuric acid.
By using above-mentioned technical proposal, so that the acidity of catalyst is extremely strong, so that the better effect of catalysis open loop, is improved
Reaction rate and reactivity.
The present invention is further arranged to: the chlorinating agent includes ethanolic hydrogen chloride solution, thionyl chloride, sulfonic acid chloride, tri-chlorination
Phosphorus.
By using above-mentioned technical proposal, it is soluble in the characteristic in alcohol using above-mentioned chlorinating agent, so that generating free chlorine
The rate of ion is very fast, so that chlorine ion concentration is higher, improves the activity of chlorination reaction, so that the chloro- 2- amino of (S) -4-
Butyrate yield is higher.
The present invention is further arranged to: the synchronous generation hydrogen chloride of chlorinating agent can be added dropwise in the chlorination reaction in methanol solution
It is carried out in alcoholic solution.
By using above-mentioned technical proposal, so that the rate for generating free chloride ion is very fast, so that chloride ion is dense
Degree is higher, the activity of chlorination reaction is improved, so that the chloro- 2-amino-butyric acid ester yield of (S) -4- is higher.
In conclusion the invention has the following advantages:
1. therefore butyrolactone structure can realize that synchronous open loop is synchronous in the system of alcohol and be esterified, and under strong acid catalyst
Constantly promote chemical balance forward direction mobile, high yield obtains (S) -4- hydroxyl -2-amino-butyric acid ester；
2. being directly catalyzed esterification by ring opening for substituted butyrolactone, the hydroxyl base contained by the intermediate after esterification by ring opening
Group is easier to be chlorinated and obtains the chloro- 2-amino-butyric acid ester of (S) -4- in high yield；
3. the chloro- 2-amino-butyric acid ester of (S) -4- very easily can obtain (S) -4- chloro- 2- (methoxy carbonyl by amido protecting
Base imino group) methyl butyrate is with the synthesis for L-glufosinate-ammonium.
Specific embodiment
With reference to embodiments, invention is further described in detail.
Embodiment 1
(S) -4- hydroxyl -2-amino-butyric acid methyl esters preparation method, by 30 grams of (S) -2- amino butyrolactone hydrochlorides
(0.218mol) is added in 250ml methanol, is slowly added dropwise and sulfuric acid 2ml is added, be added dropwise, and stirring is warming up to reflux, and about 5
Material solids all dissolve after minute.Continue back flow reaction 8 hours, HPLC tracks to raw material lower than 1%, stops reaction.
It controls thickening temperature and is not higher than 60 DEG C, reaction solution rotary evaporation is concentrated, 78 grams of colourless oil liquids of crude product are obtained,
Measurement contains (S) -4- hydroxyl -37.6 grams of 2-amino-butyric acid methyl esters, and the yield 95.2%. crude product does not need purification process can be straight
It connects for reacting in next step.
Embodiment 2
(S) solvent dilution, control is added in the preparation method of the chloro- 2-amino-butyric acid methyl esters of -4-, the solution that embodiment 1 is obtained
Temperature processed is 15-25 DEG C, stirs and is added dropwise thionyl chloride (53.6g, 0.45mol), is added dropwise and continues to be stirred to react 15 hours,
It is lower than 2% to intermediate hydroxyl object content, stops reaction.Reaction solution is measured, object must be measured as 29.2g, yield 75%.
Embodiment 3
(S) -4- hydroxyl -2-amino-butyric acid ethyl ester preparation method such as the method for embodiment 1, but methanol is replaced with
Ethyl alcohol, reflux time are 24 hours, (S) -4- hydroxyl -2- ammonia containing 93.5% yield in the colourless crude product that precipitation obtains
Base ethyl butyrate.
Embodiment 4
(S) -4- hydroxyl -2-amino-butyric acid methyl esters preparation method such as the method for embodiment 1, but catalyst is replaced
For 4 grams of p-methyl benzenesulfonic acid, reflux time is 16 hours, and precipitation obtains crude product, (S) -4- hydroxyl -2-amino-butyric acid ethyl ester
Yield is 91.6%.
Embodiment 5
(S) preparation method of the chloro- 2-amino-butyric acid ethyl ester of -4-, such as the method for embodiment 2, (S)-that embodiment 3 is obtained
4- hydroxyl -2-amino-butyric acid EtOAc chlorination in ethanol, obtains the target product of 85% yield.
Embodiment 6
120 grams of (S) -2- amino butyrolactone hydrochlorides (0.87mol) are added in 1200ml dehydrated alcohol, is added dropwise and sulphur is added
Sour 20ml, is added dropwise, and stirring is warming up to reflux, and material solids all dissolve after about 20 minutes.Continue back flow reaction 20
Hour, HPLC tracks to raw material lower than 1%, stops reaction.
Reaction solution ice water is cooled to 10 DEG C, temperature is controlled at 10-20 DEG C, thionyl chloride 200g is added dropwise in about 1 hour
(1.65mol), is added dropwise insulated and stirred 2 hours, is slowly warming up to 50 DEG C, continues stirring 4 hours, and HPLC monitoring raw material is less than
1.5%, stop reaction.
Resulting material is depressurized into precipitation, obtains pale yellow paste.400ml toluene is added, stirred crystallization is obtained by filtration
(S) the chloro- 2-amino-butyric acid carbethoxy hydrochloride 142g of -4-, total recovery 80.6%.
It can be obtained according to embodiment 1- embodiment 6, (S) -4- hydroxyl -2-amino-butyric acid ester and the chloro- 2- amino fourth of (S) -4-
The yield of acid esters is higher.
The embodiment of present embodiment is presently preferred embodiments of the present invention, not limits protection of the invention according to this
Range, therefore: the equivalence changes that all structures under this invention, shape, principle are done, should all be covered by protection scope of the present invention it
It is interior.
Claims (9)
1. the preparation method of one kind chloro- 2-amino-butyric acid ester of (S) -4-, it is characterized in that: (S) -2- amino butyrolactone under acid catalysis
Corresponding S- homoserine ester is obtained by ring opening alcoholysis, then obtains target product by the chlorination of chlorinating agent, reaction equation is such as
Under:
2. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 1, it is characterized in that: the reaction equation
Middle R is one of the alkyl of C1-C4.
3. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 2, it is characterized in that: the reaction equation
Middle R is methyl or ethyl.
4. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 3, it is characterized in that: the reaction equation
Middle R is ethyl.
5. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 1, it is characterized in that: the catalyst
For inorganic sulfonic acid or organic sulfonic acid.
6. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 5, it is characterized in that: the catalyst
For the concentrated sulfuric acid, benzene sulfonic acid, p-methyl benzenesulfonic acid, methane sulfonic acid, ethylsulfonic acid.
7. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 6, it is characterized in that: the catalyst
For sulfuric acid.
8. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 1, it is characterized in that: the chlorinating agent
Including ethanolic hydrogen chloride solution, thionyl chloride, sulfonic acid chloride, phosphorus trichloride.
9. the preparation method of the chloro- 2-amino-butyric acid ester of (S) -4- according to claim 8, it is characterized in that: the chlorination is anti-
It should can be carried out in synchronous generate in ethanolic hydrogen chloride solution of methanol solution middle or low price chlorinating agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811302666.7A CN109369432B (en) | 2018-11-02 | 2018-11-02 | Preparation method of (S) -4-chloro-2-aminobutyrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811302666.7A CN109369432B (en) | 2018-11-02 | 2018-11-02 | Preparation method of (S) -4-chloro-2-aminobutyrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109369432A true CN109369432A (en) | 2019-02-22 |
| CN109369432B CN109369432B (en) | 2021-06-25 |
Family
ID=65397039
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811302666.7A Active CN109369432B (en) | 2018-11-02 | 2018-11-02 | Preparation method of (S) -4-chloro-2-aminobutyrate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109369432B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110386882A (en) * | 2019-08-12 | 2019-10-29 | 利尔化学股份有限公司 | (S) preparation method of the chloro- 2- of -4- ((ethoxy carbonyl) amino) ethyl butyrate |
| CN110845347A (en) * | 2019-11-21 | 2020-02-28 | 利尔化学股份有限公司 | Preparation method of chloro-homoserine alkyl ester |
| CN114163471A (en) * | 2020-09-11 | 2022-03-11 | 南京华狮新材料有限公司 | Preparation method of long-chain homoserine derivative |
| CN115093339A (en) * | 2022-07-20 | 2022-09-23 | 永农生物科学有限公司 | Synthetic method of L-glufosinate-ammonium intermediate |
| WO2023051768A1 (en) * | 2021-09-30 | 2023-04-06 | 利尔化学股份有限公司 | Methods for preparing (s)-4-chloro-2-aminobutyric acid hydrochloride and (s)-4-chloro-2-aminobutyrate |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5705333A (en) * | 1994-08-05 | 1998-01-06 | The Regents Of The University Of California | Peptide-based nucleic acid mimics(PENAMS) |
| US5710129A (en) * | 1995-02-23 | 1998-01-20 | Ariad Pharmaceuticals, Inc. | Inhibitors of SH2-mediated processes |
| CN1064671C (en) * | 1996-08-06 | 2001-04-18 | 中国石油化工总公司上海石油化工研究院 | Synthetic method for gamma halogenated butyric ester |
| GB0031179D0 (en) * | 2000-12-21 | 2001-01-31 | Glaxo Group Ltd | Nitric oxide synthase inhibitors |
| US7399766B2 (en) * | 2004-08-18 | 2008-07-15 | Parion Sciences, Inc. | Soluble amide & ester pyrazinoylguanidine sodium channel blockers |
| US20070021439A1 (en) * | 2005-07-25 | 2007-01-25 | Parion Sciences, Inc. | Methods of reducing risk of infection from pathogens with soluble amide and ester pyrazinoylguanidine sodium channel blockers |
| EP2225238B1 (en) * | 2007-11-29 | 2014-09-03 | Boehringer Ingelheim International GmbH | Derivatives of 6,7-dihydro-5h-imidazoý1,2- ¨imidazole-3- carboxylic acid amides |
| WO2013173583A1 (en) * | 2012-05-16 | 2013-11-21 | Cancer Targeted Technology, Llc | Psma inhibitors |
| CN104356099B (en) * | 2014-11-19 | 2016-05-11 | 郑州大学 | Homoserine lactone compounds, its preparation method and application thereof |
| GB201504689D0 (en) * | 2015-03-19 | 2015-05-06 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| DK3337791T3 (en) * | 2015-08-17 | 2022-10-24 | Univ Health Network | INHIBITORS OF PEPTIDYLARGINE DEIMINASE (PAD) ENZYMES AND USES THEREOF |
| CN106631777B (en) * | 2016-11-30 | 2019-02-19 | 浙江大学 | Synthesize γ-chlorobutanoate method |
| SI3612531T1 (en) * | 2017-04-18 | 2022-11-30 | Shanghai Fochon Pharmaceutical Co., Ltd. | Apoptosis-inducing agents |
-
2018
- 2018-11-02 CN CN201811302666.7A patent/CN109369432B/en active Active
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110386882A (en) * | 2019-08-12 | 2019-10-29 | 利尔化学股份有限公司 | (S) preparation method of the chloro- 2- of -4- ((ethoxy carbonyl) amino) ethyl butyrate |
| CN110845347A (en) * | 2019-11-21 | 2020-02-28 | 利尔化学股份有限公司 | Preparation method of chloro-homoserine alkyl ester |
| WO2021098712A1 (en) * | 2019-11-21 | 2021-05-27 | 利尔化学股份有限公司 | Preparation method for chlorohomoserine alkyl ester |
| CN110845347B (en) * | 2019-11-21 | 2021-10-15 | 利尔化学股份有限公司 | Preparation method of chloro-homoserine alkyl ester |
| CN114163471A (en) * | 2020-09-11 | 2022-03-11 | 南京华狮新材料有限公司 | Preparation method of long-chain homoserine derivative |
| WO2023051768A1 (en) * | 2021-09-30 | 2023-04-06 | 利尔化学股份有限公司 | Methods for preparing (s)-4-chloro-2-aminobutyric acid hydrochloride and (s)-4-chloro-2-aminobutyrate |
| CN115093339A (en) * | 2022-07-20 | 2022-09-23 | 永农生物科学有限公司 | Synthetic method of L-glufosinate-ammonium intermediate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109369432B (en) | 2021-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109369432A (en) | (S) preparation method of the chloro- 2-amino-butyric acid ester of -4- | |
| CN103012525B (en) | Method for synthesizing emamectin benzoate | |
| Heydari et al. | Trifluoroethanol as a metal-free, homogeneous and recyclable medium for the efficient one-pot synthesis of α-amino nitriles and α-amino phosphonates | |
| CN104530040B (en) | Novel method for synthesizing 1,2,3-thiadiazole-5-formamidine compound | |
| BR102018002949B1 (en) | method of preparing azoxystrobin intermediates | |
| US8492542B2 (en) | Method for producing bicyclic guanidines by use of a cyclic thiourea | |
| KR101684044B1 (en) | Methods for producing 1,5,7-triazabicyclo[4.4.0] dec-5-ene by reaction of a disubstituted carbodiimide and dipropylene triamine | |
| CN109942622A (en) | A kind of preparation method of the phosphate flame retardant containing unsaturated hydrocarbons | |
| CN101270062B (en) | Methylene technique for producing acetochlor | |
| CN105111103A (en) | Method for preparing cyanophenol and derivative thereof | |
| CN109776605B (en) | Synthesis method of glufosinate-ammonium | |
| WO2019179287A2 (en) | Preparation method for 2,4-dichlorophenoxyacetic acid or salt thereof | |
| TWI388545B (en) | A method for preparing a catalytic composition of amide and a method for producing amide | |
| CN108276356B (en) | Preparation method of 3, 5-disubstituted thiazolidine-2-thioketone compound | |
| US20110077426A1 (en) | Method for synthesis of o-diphenylphosphinobenzoic acid | |
| US11401288B2 (en) | Beta-amino phosphonic acid derivative and preparation method therefor | |
| CN109897064A (en) | A kind of 3- indyl -3-(p diethylaminobenzoic acid ester group) Oxoindole compound preparation method | |
| CN102432470A (en) | Novel production process of chlorthal | |
| CN115093339A (en) | Synthetic method of L-glufosinate-ammonium intermediate | |
| CN109761928B (en) | Preparation method of 2, 6-dichlorobenzoxazole | |
| CN107513047A (en) | Microwave assisting method synthesizes the friendly process of BPTA | |
| CN106518865A (en) | Method for preparing 1-alkenyl indolizine derivative | |
| CN108727428B (en) | β -aminophosphonic acid derivatives and process for their preparation | |
| CN103288693A (en) | Method for preparing 1-thiol pyrene and intermediate compound thereof | |
| CN110791467B (en) | Recombinant bacterium for producing acetylacetone and construction method and application thereof |
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 |