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Process for preparing optical purity tetrahydrofuran-2-aminic acid

A technology for the preparation of tetrahydrofuran, which is applied in the direction of organic chemistry, can solve the problems of resolution agent toxicity, environmental pollution, low yield, etc., and achieve the effects of convenient recovery and recycling, improved optical purity, and simple process methods

Inactive Publication Date: 2005-06-01
CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But it uses very toxic and expensive strychnine (Brucine dihydrate) as a resolution agent, its e.e. value can reach 94%, but the yield is very low, only 20%, and the recovery rate of the resolution agent is also low
Japanese patent [JP 01,216,983(1989)], European patent [EP382,506(1990)] and U.S. patent [US 4,985,575(1991)] use α-methylbenzylamine-type optically active amines as resolving agents, e.e. It can reach 99%, the toxicity of the resolving agent is low, and it can be recovered well, but the disadvantage is that the salt generated by amine and acid needs to be recrystallized many times to obtain tetrahydrofuran-2-carboxylic acid with high optical purity , the highest yield is only 30%
However, all the resolution methods mentioned above can only obtain optically pure isomers of one configuration with a resolving agent of one configuration in actual operation, and cause the abandonment of another isomer, which can neither effectively utilize raw materials, pollute the environment

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] 162 grams (0.431mol) of D-DBTA and 24 grams (0.431mol) of CaO were added to 200 ml of methanol, then 50 grams (0.431mol) of (±)-tetrahydrofuran-2-carboxylic acid was added, and 300 ml of water was slowly added dropwise, Reflux for 1 hour, cool, and a solid precipitates out. Filtration and drying of the solid yielded 120 g of white crystals. The mother liquor was adjusted to pH=1 by adding acid, the resolving agent was separated out, filtered, and recovered; the filtrate was extracted with 5×30ml ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain (S)-tetrahydrofuran-2- Formic acid 18.4 g, optical purity 87% e.e., yield 36.8%.

[0020] The above white crystals were recrystallized in 800 ml of methanol and 200 ml of water, and filtered to obtain 101 g of white crystals. Slowly add hydrochloric acid dropwise to the flask containing the crystals, adjust to pH = 1, separate out the solid resol...

Embodiment 2

[0022] Mix 1.16 grams (0.01 mol) of 87% e.e. (S)-tetrahydrofuran-2-carboxylic acid obtained in the mother liquor of Example 1 with 0.3 grams (0.005 mol) of ethylenediamine to form a salt, add 10 ml of absolute ethanol, and heat to reflux. After dissolving, stand to cool to precipitate solid, and filter to obtain 1.431 g of white solid. After recrystallization, add the solid to 15ml 1M sodium hydroxide solution and stir for 10 minutes, wash with 3×15ml ethyl acetate, add 17ml 1M hydrochloric acid to the aqueous phase and stir, extract with 3×15ml ethyl acetate, and combine the organic phases , dried over anhydrous sodium sulfate, and evaporated to dryness to obtain 0.93 g of (S)-tetrahydrofuran-2-carboxylic acid with an optical purity of 89% e.e. and a yield of 80.17%.

Embodiment 3

[0024]Mix 1.16 g (0.01 mol) of 87% e.e. (S)-tetrahydrofuran-2-carboxylic acid obtained in the mother liquor of Example 1 with 0.99 g (0.01 mol) of cyclohexylamine to form a salt, then add 4 ml of methanol, heat to reflux, and completely dissolve , cooled to precipitate a solid, and filtered to obtain 0.795 g of a white solid. After recrystallization, add the solid to 15ml 1M sodium hydroxide solution and stir for 10 minutes, wash with 3×15ml ethyl acetate, add 17ml 1M hydrochloric acid to the aqueous phase and stir, extract with 3×15ml ethyl acetate, and combine the organic phases , dried over anhydrous sodium sulfate, and evaporated to dryness to obtain 0.35 g of (S)-tetrahydrofuran-2-carboxylic acid with an optical purity of 90.1% e.e. and a yield of 30.17%.

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Abstract

A new process for the preparation of optically pure tetrahydrofuran-2-carboxylic acid, using a configuration of tartaric acid derivative O, O'-diaryl formyl tartaric acid to split tetrahydrofuran-2-carboxylic acid, crystallization and recrystallization of the reaction product, After obtaining a configuration of optically pure tetrahydrofuran-2-carboxylic acid, the other isomer in the mother liquor of the above crystallization operation is salted with achiral amine, and the optical purity reaches 89-99% after crystallization and recrystallization Between e.e.; the isomer of another configuration with an optical purity lower than 98% e.e. in the mother liquor of the above crystallization operation is heated under alkaline conditions to racemize to form a racemate, and then repeat the resolution , and the above steps until two configurations of optically pure tetrahydrofuran-2-carboxylic acid are obtained. Thus, the resolution yield of the other isomer can be increased to more than 50%. The invention has the advantages of simple process, easy-to-obtain raw materials, high yield, recycling of the resolving agent and another configuration of tetrahydrofuran-2-carboxylic acid, reducing the preparation cost and realizing environmental protection; it is beneficial to realize large-scale industrial production and meet the requirements of people's needs for it.

Description

technical field [0001] The invention belongs to the field of organic synthesis, specifically a method for obtaining two configurations of optically pure tetrahydrofuran-2-carboxylic acid and R- or S-tetrahydrofuran-2-carboxylic acid using a chemical method for racemization by using a resolution agent of one configuration . Background technique [0002] Optically pure tetrahydrofuran-2-carboxylic acid is an important intermediate, which is widely used in many fields such as medicine and chemical industry. Pure tetrahydrofuran-2-carboxylic acid was used as an intermediate for synthetic preparation. Because optically pure tetrahydrofuran-2-carboxylic acid can be used in various fields, its preparation method has attracted people's attention. The existing methods for splitting the racemate mainly include 1. mechanical method; 2. biochemical method; 3. chemical method. In terms of the racemization of the racemate tetrahydrofuran-2-carboxylic acid by chemical methods, P.C.Belan...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D307/24
Inventor 廖建胡昱朱槿邓金根刘晖雷三忠
Owner CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI
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