CN105001104A - Method for preparing S-6-methoxyl-1-amino indan - Google Patents
Method for preparing S-6-methoxyl-1-amino indan Download PDFInfo
- Publication number
- CN105001104A CN105001104A CN201510529753.6A CN201510529753A CN105001104A CN 105001104 A CN105001104 A CN 105001104A CN 201510529753 A CN201510529753 A CN 201510529753A CN 105001104 A CN105001104 A CN 105001104A
- Authority
- CN
- China
- Prior art keywords
- aminoidan
- methoxyl group
- methoxyl
- amino indan
- split
- 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
Abstract
The invention discloses a method for preparing S-6-methoxyl-1-amino indan through splitting racemic 6-methoxyl-1-amino indan by D-mandelic acid. The method concretely comprises the following steps that the D-mandelic acid is dissolved into alcoholic solvents; a certain amount of alcoholic solution of 6-methoxyl-1-amino indan is dripped at a certain temperature; the materials are stirred for reaction for certain time; through operations of cooling crystallization, filtering and the like, the D-mandelate of S-6-methoxyl-1-amino indan is obtained; salt recrystallization is carried out once; then, the materials are dissolved into a certain quantity of water; alkali is added to regulate the pH value to 11 to 13; extracting agents are added; liquid separation, drying and concentration are carried out to obtain the S-6-methoxyl-1-amino indan; the ee value of the S-6-methoxyl-1-amino indan is higher than 99; the yield reaches higher than 30 percent. The method has the advantages that the conditions are mild; the operation is simple; the product yield is high; the optical purity is high, and the like. The method is particularly suitable for being used for industrial production of the S-6-methoxyl-1-amino indan.
Description
Technical field
The present invention relates to a kind of fractionation preparation method of optical homochiral compound, particularly relate to a kind of method that the D-of utilization amygdalic acid resolution of racemic 6-methoxyl group-1-aminoidan prepares S-6-methoxyl group-1-aminoidan.
Background technology
S-6-methoxyl group-1-aminoidan is the very important chiral medicinal intermediate of a class.In existing 6-methoxyl group-1-aminoidan relevant report, then rarely has report about how preparing optical purity S-6-methoxyl group-1-aminoidan.Chemical resolution method is a kind of a kind of method for splitting being relatively applicable to suitability for industrialized production, and how obtaining a kind of efficient, inexpensive chemical resolution method is problem to be solved by this invention.
Summary of the invention
The object of this invention is to provide the method that the low and simple fractionation of a kind of cost obtains optical purity S-6-methoxyl group-1-aminoidan.The present invention utilizes D-amygdalic acid to split racemization 6-methoxyl group-1-aminoidan, and to obtain the method concrete operations of S-6-methoxyl group-1-aminoidan as follows: be dissolved in alcoholic solvent by D-amygdalic acid, drip the alcoholic solution of a certain amount of 6-methoxyl group-1-aminoidan at a certain temperature, stirring reaction certain hour, through crystallisation by cooling, to filter etc. and operate to obtain the D-mandelate of S-6-methoxyl group-1-aminoidan, salt recrystallization is once dissolved in certain water gaging afterwards, adding alkali regulates pH value to 11-13, add extraction agent, separatory, dry, concentrate to obtain S-6-methoxyl group-1-aminoidan, its ee value is more than 99, and yield reaches more than 30%.
According to described, the present invention's raw material used is racemization 6-methoxyl group-1-aminoidan, and resolving agent is D-amygdalic acid, and the molar ratio of raw material and resolving agent is 1:1.0 ~ 2.0; The solvent used according to described fractionation S-6-methoxyl group-1-aminoidan is methyl alcohol or ethanol, and the mass ratio that feeds intake of raw material and solvent is 10 ~ 30; The organic solvent used according to described extraction is methylene dichloride or ethyl acetate.
Of the present invention effective: reaction process of the present invention is selected rationally, develop a kind of method that resolution 6-methoxyl group-1-aminoidan prepares S-6-methoxyl group-1-aminoidan, method for splitting is simple, effective, resolving chiral purity can reach more than 99%, and yield has about 40%.Fractionation preparation for optical purity S-6-methoxyl group-1-aminoidan provide referentially to save time, economic, preparation method efficiently.
Specific implementation method:
Embodiment 1
(1) 6-methoxyl group-1-aminoidan splits
In 1000ml round-bottomed flask, add 22.8G(0.15mol) D-amygdalic acid, 300ml methyl alcohol, magnetic agitation, at 55 DEG C drip be dissolved in 16.3G(0.1mol in 100ml methanol solvate) 6-methoxyl group-1-aminoidan, back flow reaction 1.5h.Naturally cooling, is chilled to room temperature, separates out white precipitate, and suction filtration obtains white and product 13.4g.Use 150ml recrystallizing methanol, obtain the D-mandelate that 12.1g refines S-6-methoxyl group-1-aminoidan, yield is 40.7%.
(2) S-6-methoxyl group-1-aminoidan is prepared
The D-mandelate 12.1g of upper step gained S-6-methoxyl group-1-aminoidan is dissolved in 200ml water, drip 40% sodium hydroxide solution and regulate pH value to 12,3 times are extracted with methylene dichloride (100ml, 50ml, 50ml), dichloromethane layer merges, with water (50ml), saturated brine (50ml) respectively washing once, anhydrous sodium sulfate drying, filtration, concentratedly to obtain S-6-methoxyl group-1-aminoidan 6.0g, yield is 36.8%, ee value is 99.4%.
Embodiment 2
(1) 6-methoxyl group-1-aminoidan splits
In 1000ml round-bottomed flask, add 18.2G(0.12mol) D-amygdalic acid, 200ml ethanol, magnetic agitation, at 50 DEG C drip be dissolved in 16.3G(0.1mol in 100ml alcohol solvent) 6-methoxyl group-1-aminoidan, back flow reaction 2h.Naturally cooling, is chilled to room temperature, separates out white precipitate, and suction filtration obtains white and product 14.4g.Use 160ml recrystallizing methanol, obtain the D-mandelate that 13.1g refines S-6-methoxyl group-1-aminoidan, yield is 44.1%.
(2) S-6-methoxyl group-1-aminoidan is prepared
The D-mandelate 13.1g of upper step gained S-6-methoxyl group-1-aminoidan is dissolved in 200ml water, drip ammonia soln and regulate pH value to 13,3 times are extracted by ethyl acetate (100ml, 50ml, 50ml), ethyl acetate layer merges, with water (50ml), saturated brine (50ml) respectively washing once, anhydrous sodium sulfate drying, filtration, concentratedly to obtain S-6-methoxyl group-1-aminoidan 6.6g, yield is 40.5%, ee value is 99.2%.
Claims (5)
1. the present invention utilizes D-amygdalic acid fractionation racemization 6-methoxyl group-1-aminoidan to obtain the method for S-6-methoxyl group-1-aminoidan, concrete operations are as follows: be dissolved in alcoholic solvent by D-amygdalic acid, drip the alcoholic solution of a certain amount of 6-methoxyl group-1-aminoidan at a certain temperature, stirring reaction certain hour, through crystallisation by cooling, to filter etc. and operate to obtain the D-mandelate of S-6-methoxyl group-1-aminoidan, salt recrystallization is once dissolved in certain water gaging afterwards, adding alkali regulates pH value to 11-13, add extraction agent, separatory, dry, concentrate to obtain S-6-methoxyl group-1-aminoidan, its ee value is more than 99, and yield reaches more than 30%.
2. split the method preparing S-6-methoxyl group-1-aminoidan according to claim 1, it is characterized in that: it is racemization 6-methoxyl group-1-aminoidan that the present invention splits raw material used, resolving agent is D-amygdalic acid, and the molar ratio of raw material and resolving agent is 1:1.0 ~ 2.0.
3. split the method preparing S-6-methoxyl group-1-aminoidan according to claim 1, it is characterized in that: the solvent splitting S-6-methoxyl group-1-aminoidan used is methyl alcohol or ethanol, and the mass ratio that feeds intake of raw material and solvent is 10 ~ 30.
4. split the method preparing S-6-methoxyl group-1-aminoidan according to claim 1, it is characterized in that: extracting organic solvent used is methylene dichloride or ethyl acetate.
5. split the method preparing S-6-methoxyl group-1-aminoidan according to claim 1, it is characterized in that: the alkali used that alkalizes is NaOH solution or ammonia soln.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510529753.6A CN105001104A (en) | 2015-08-26 | 2015-08-26 | Method for preparing S-6-methoxyl-1-amino indan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510529753.6A CN105001104A (en) | 2015-08-26 | 2015-08-26 | Method for preparing S-6-methoxyl-1-amino indan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105001104A true CN105001104A (en) | 2015-10-28 |
Family
ID=54374019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510529753.6A Pending CN105001104A (en) | 2015-08-26 | 2015-08-26 | Method for preparing S-6-methoxyl-1-amino indan |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105001104A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996021640A1 (en) * | 1995-01-12 | 1996-07-18 | Teva Pharmaceutical Industries, Ltd. | Optically active aminoindane derivatives and preparation thereof |
| US5639913A (en) * | 1994-01-10 | 1997-06-17 | Teva Pharmaceutical Industries, Ltd. | Method for preparing optically active 1-aminoindan derivatives |
-
2015
- 2015-08-26 CN CN201510529753.6A patent/CN105001104A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5639913A (en) * | 1994-01-10 | 1997-06-17 | Teva Pharmaceutical Industries, Ltd. | Method for preparing optically active 1-aminoindan derivatives |
| WO1996021640A1 (en) * | 1995-01-12 | 1996-07-18 | Teva Pharmaceutical Industries, Ltd. | Optically active aminoindane derivatives and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| WILLIAM B. LAWSON ET AL.: "Specificity in the Alkylation of Methionine at the Active Site of α-Chymotrypsin by Aromatic α-Bromo Amides", 《BIOCHEMISTRY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104193635A (en) | Synthesis method of pregabalin | |
| CN101704755A (en) | Method for preparing p-tert-butylbenzylamine | |
| CN105130794A (en) | Method for preparing S-4-methoxymandelic acid through splitting S-1-phenylethylamine | |
| CN104557674B (en) | The preparation method of the hydroxy piperidines of one kind (S) N Boc 3 | |
| CN101407465A (en) | Method for preparing optical pure 1-(1-naphthyl)ethylamine by separation | |
| CN103833562B (en) | A kind of preparation method of asymmetric synthesis lyrica | |
| CN105001104A (en) | Method for preparing S-6-methoxyl-1-amino indan | |
| CN104557677A (en) | Chemical resolution preparation method for optical pure 2-pipecolic acid | |
| CN101723826B (en) | Preparation method of trans-D-chrysanthemic acid | |
| CN105085285A (en) | Method for preparing R-6-methoxy-1-aminoindane | |
| CN103102280B (en) | The preparation method of optical voidness 1-(alpha-amido benzyl)-beta naphthal | |
| CN105085243A (en) | Preparing method of (S)-(-)-4-bromine mandelic acid | |
| CN104725259B (en) | Preparation method for levodopa intermediate derivative | |
| CN103787921B (en) | A kind of method preparing trans 1, the 2-ring diamines of high-optical-purity | |
| CN102757367A (en) | Splitting process of racemic ethyl benzene sulfonic acid | |
| CN105061219A (en) | Method for preparing S-1-aminoindane | |
| CN105037169A (en) | Method for preparing S-5-chloro-1-aminoindane | |
| CN105085244A (en) | Preparing method of (R)-(+)-4-bromomandelic acid | |
| CN105061228A (en) | Method for preparing R-6-hydroxy-1-aminoindane | |
| CN105085234A (en) | Preparing method of (R)-(-)-4-chloromandelic acid | |
| CN101314574B (en) | Process for synthesizing acylations enamine | |
| CN104591939B (en) | A kind of method preparing xenyl acrylic acid ether compound | |
| CN105175273A (en) | Method for preparing (S)- 6-hydroxy-1-aminoindan | |
| CN105111091A (en) | Method for preparing S-3-methyl-1-aminoindane | |
| CN105085245A (en) | Preparing method of (R)-(+)-4-fluoromandelic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20151028 |