CN113024391A - Preparation of (S) - (-) -alpha-methylaminopropiophenone - Google Patents
Preparation of (S) - (-) -alpha-methylaminopropiophenone Download PDFInfo
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- CN113024391A CN113024391A CN202110381839.4A CN202110381839A CN113024391A CN 113024391 A CN113024391 A CN 113024391A CN 202110381839 A CN202110381839 A CN 202110381839A CN 113024391 A CN113024391 A CN 113024391A
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- China
- Prior art keywords
- ether
- solvent
- alpha
- methylaminopropiophenone
- ester
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the field of chemistry, and discloses a preparation method of (S) - (-) -alpha-methylaminopropiophenone, which comprises the steps of reacting (+/-) -alpha-methylaminopropiophenone with (2R, 3R) - (-) -tartaric acid derivatives in an alcohol ether solvent to form salts, crystallizing and filtering to obtain (S) - (-) -alpha-methylaminopropiophenone- (2R, 3R) - (-) -tartaric acid derivative salts, acidifying, alkalifying, extracting with a solvent, and distilling to remove the solvent to obtain the product (S) - (-) -alpha-methylaminopropiophenone.
Description
Technical Field
The invention relates to the field of chemistry, and discloses a preparation method of (S) - (-) -alpha-methylaminopropiophenone, which is an important medical intermediate. Splitting (+/-) -alpha-methylaminopropiophenone by using (2R, 3R) - (-) -tartaric acid derivative as a resolving agent. Dissolving the two in a mixed solvent of ester ether and alcohol ether respectively, or dissolving one in the ester ether solvent and the other in the mixed solvent of ester ether and alcohol ether, then mixing, dissolving respectively, mixing to form salt, crystallizing, filtering to obtain the product (S) - (-) -alpha-methylaminopropiophenone- (2R, 3R) - (-) -tartaric acid derivative, acidifying, alkalinizing, extracting with solvent, distilling to remove the solvent to obtain the product (S) - (-) -alpha-methylaminopropiophenone.
Background
The prior art for preparing (S) - (-) -alpha-methylaminopropiophenone has the defects of long production time, low efficiency, low solvent boiling point and difficult recovery, and a new method is urgently needed, so the production time is shortened, and the production cost is reduced.
Disclosure of Invention
1. The invention aims to improve the efficiency of producing (S) - (-) -alpha-methylaminopropiophenone, shorten the production time and reduce the production cost, and provides a method for separating by ester ether solvents and alcohol ether solvents or mixed solvents thereof, wherein (2R, 3R) - (-) -dibenzoyl tartaric acid and monohydrate, (2R, 3R) - (-) -di-p-methylbenzoyl tartaric acid and monohydrate, (2R, 3R) - (-) -di-m-methylbenzoyl tartaric acid and monohydrate, (2R, 3R) - (-) -di-o-methylbenzoyl tartaric acid and monohydrate, (2R, 3R) - (-) -diacetyl tartaric acid and monohydrate, (2R, 3R) - (-) -di-p-methoxybenzoyl tartaric acid and a hydrate are used as resolving agents to resolve (+/-) -alpha-methylaminopropiophenone. According to the method, the resolution and crystallization can be completed in a short time, and the resolution efficiency is high. In addition, the alcohol ether solvent has a high boiling point, such as the boiling point of ethylene glycol methyl ether of 124-. Respectively dissolving (+/-) -alpha-methylaminopropiophenone in ester ether solvent, alcohol ether solvent or their mixture. Dissolving (2R, 3R) - (-) -tartaric acid derivative with ester ether solvent, alcohol ether solvent or their mixture, adding the solution into (+/-) -alpha-methylaminopropiophenone solution, stirring for a while in a greenhouse to obtain precipitate, filtering, and drying to obtain (S) - (-) -alpha-methylaminopropiophenone- (2R 3R) - (-) -tartaric acid derivative salt.
Dissolving the salt in water, adjusting pH to 11-12 with sodium hydroxide aqueous solution, extracting with diethyl ether, and distilling off diethyl ether to obtain (S) - (-) -alpha-methylaminopropiophenone.
The solvent used for resolution is ester ether and alcohol ether solvent or their mixture solvent.
The alcohol ether solvents include all compounds having both ether bond and hydroxyl group, such as ethylene glycol methyl ether, ethylene glycol ethyl ether, propylene glycol methyl ether, propylene glycol ethyl ether, are not limited to the above names, but include all alcohol ether solvents.
Ester ethers refer to all ester solvents, all ether solvents.
The material is added in any proportion of the weight of the solvent.
The salt formation temperature is preferably room temperature, and may be any temperature.
The salt formation time is any time, preferably 1 to 4 hours.
Detailed description of the preferred embodiment 1
Weighing 4.09g (+/-) -alpha-methylaminopropanone and dissolving in a 15ml ethyl acetate A bottle for later use. Dissolving 4.49g of (2R, 3R) - (-) -dibenzoyltartaric acid in 5ml of ethyl acetate and 3ml of ethylene glycol methyl ether B bottle, adding the solution in the B bottle into the solution in the A bottle under stirring, stirring for 2 hours, and filtering to obtain 5.89g of (S) - (-) -alpha-methylaminopropiophenone- (2R, 3R) - (-) -dibenzoyltartaric acid as a white solid.
Dissolving 5.89g of the obtained product in 20ml of water, adjusting the pH to 11-12 by using 10 percent aqueous solution of sodium hydroxide, adding 20ml of ether, extracting and separating, and evaporating the ether to obtain the (S) - (-) -alpha-methylaminopropiophenone product.
Claims (6)
- A process for preparing (S) - (-) -alpha-methylaminopropiophenone, which comprises dissolving (+ -) -alpha-methylaminopropiophenone and (2R, 3R) - (-) -tartaric acid derivative in a mixed solvent of ester ether and alcohol ether, respectively, or dissolving one substance in ester ether solvent and the other substance in a mixed solvent of ester ether and alcohol ether, mixing, crystallizing the salt of (S) - (-) -alpha-methylaminopropiophenone- (2R, 3R) - (-) -tartaric acid derivative in the solvent, filtering to obtain a solid product, (S) - (-) -alpha-methylaminopropiophenone- (2R, 3R) - (-) -tartaric acid derivative, the (S) - (-) -alpha-methylaminopropiophenone product is obtained by alkalization, solvent extraction and solvent distillation.
- 2. According to claim 1, ester ethers mean all ester solvents, all ether solvents.
- 3. According to claim 1, the alcohol ether type solvent includes all compounds having both ether bond and hydroxyl group, such as ethylene glycol methyl ether, ethylene glycol ethyl ether, propylene glycol methyl ether, propylene glycol ethyl ether, not limited to the above names, but includes all alcohol ether type solvents.
- 4. According to claim 1, the ester ether and the alcohol ether solvent are mixed in an arbitrary ratio.
- 5. The method of claim 1, wherein the solvent is used in any weight ratio to (±) - α -methylaminopropanone.
- 6. The method of claim 1, wherein the tartaric acid derivative is selected from the group consisting of (2R, 3R) - (-) -dibenzoyltartaric acid and a monohydrate, (2R, 3R) - (-) -di-p-methylbenzoyltartaric acid and a monohydrate, (2R, 3R) - (-) -di-o-methylbenzoyltartaric acid and a monohydrate, (2R, 3R) - (-) -diacetyltartaric acid and a monohydrate, (2R, 3R) - (-) -di-p-methoxybenzoyltartaric acid and a monohydrate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110381839.4A CN113024391A (en) | 2021-04-09 | 2021-04-09 | Preparation of (S) - (-) -alpha-methylaminopropiophenone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110381839.4A CN113024391A (en) | 2021-04-09 | 2021-04-09 | Preparation of (S) - (-) -alpha-methylaminopropiophenone |
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| Publication Number | Publication Date |
|---|---|
| CN113024391A true CN113024391A (en) | 2021-06-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN202110381839.4A Pending CN113024391A (en) | 2021-04-09 | 2021-04-09 | Preparation of (S) - (-) -alpha-methylaminopropiophenone |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1583714A (en) * | 2004-06-02 | 2005-02-23 | 上海医药工业研究院 | Preparation of [(S)-(-)-alpha-methylamino phenylketone]2.(2R,3R)-tartaric acid derivative |
| CN104119240A (en) * | 2013-04-23 | 2014-10-29 | 中国人民解放军军事医学科学院毒物药物研究所 | Preparation method for (S)-(-)-alpha-methylaminopropiophenone |
| CN111233682A (en) * | 2020-03-02 | 2020-06-05 | 北京旋光普利生物医药科技开发有限公司 | Preparation of (S) - (-) - α -methylaminopropiophenone |
-
2021
- 2021-04-09 CN CN202110381839.4A patent/CN113024391A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1583714A (en) * | 2004-06-02 | 2005-02-23 | 上海医药工业研究院 | Preparation of [(S)-(-)-alpha-methylamino phenylketone]2.(2R,3R)-tartaric acid derivative |
| CN104119240A (en) * | 2013-04-23 | 2014-10-29 | 中国人民解放军军事医学科学院毒物药物研究所 | Preparation method for (S)-(-)-alpha-methylaminopropiophenone |
| CN111233682A (en) * | 2020-03-02 | 2020-06-05 | 北京旋光普利生物医药科技开发有限公司 | Preparation of (S) - (-) - α -methylaminopropiophenone |
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Application publication date: 20210625 |
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