阅读说明：本技术 一种手性氨基酸的制备方法 (Preparation method of chiral amino acid ) 是由 林金新 郭小雷 黄平 于 2019-10-09 设计创作，主要内容包括：本发明属于氨基酸技术领域,涉及一种手性氨基酸酯的制备方法。包括以下步骤：取DL-氨基酸酯2mmo1溶于10ml乙酸乙酯；取拆分剂对DL氨基酸酯溶液进行手性拆分,对手性拆分过后DL氨基酸酯溶液的滴入10ml含1mmolRTTCA的乙酸乙酯溶液,搅拌反应30~60min,有大量白色沉淀或者粘稠油状物析出,分离出固体或油状物,即为RTTCA-氨基酸酯盐。取RTTCA-氨基酸酯盐加入1.5moL/L NaOH溶液使盐分解,再用乙酸乙酯萃取,分离出光学活性氨基酸酯,其光学纯度达到58%~69%,收率达到50%以上。(The invention belongs to the technical field of amino acid, and relates to a preparation method of chiral amino acid ester, which comprises the following steps of dissolving DL-amino acid ester 2mmo1 in 10ml of ethyl acetate, taking a resolving agent to carry out chiral resolution on DL-amino acid ester solution, dripping 10ml of ethyl acetate solution containing 1mmol RTTCA into the DL-amino acid ester solution after the chiral resolution, stirring and reacting for 30 ~ 60min, separating out a large amount of white precipitate or viscous oily matter, and separating out solid or oily matter, namely RTTCA-amino acid ester salt, taking RTTCA-amino acid ester salt, adding 1.5moL/L NaOH solution into the RTTCA-amino acid ester salt to decompose salt, extracting with ethyl acetate, and separating out optically active amino acid ester, wherein the optical purity of the optically active amino acid ester reaches ~ 69%, and the yield of the optically active amino acid ester reaches more than 50%.)

1. A preparation method of chiral amino acid ester comprises the following steps:

s10, dissolving DL-amino acid ester in ethyl acetate;

s20, taking a resolving agent to carry out chiral resolution on the DL amino acid ester solution;

s30, dripping an ethyl acetate solution containing RTTCA into the DL amino acid ester solution after chiral resolution, stirring for reaction for 30 ~ 60min, precipitating a large amount of white precipitate or viscous oily matter, and filtering to separate out solid or oily matter, namely RTTCA-amino acid ester salt 1 a;

s40, washing the filtrate with NaOH and saturated saline solution sequentially;

s50, drying the washed organic layer by a drying agent, evaporating to remove the solvent to obtain the optically active amino acid ester 2a with the optical purity of 63 percent ~ 75 percent;

s60, adding 6-12 parts of RTTCA-amino acid ester salt 1a solution into NaOH solution to decompose salt;

s70, extracting with ethyl acetate to separate optically active amino acid ester 3a with optical purity of 58% ~ 69%.

2. The method of claim 1, comprising the steps of:

s10, dissolving DL-amino acid ester 2mmo1 in 10ml ethyl acetate;

s20, taking a resolving agent to carry out chiral resolution on the DL amino acid ester solution;

s30, dripping 10ml of ethyl acetate solution containing 1mmol of RTTCA into the DL amino acid ester solution after chiral resolution, stirring and reacting for 30 ~ 60min, precipitating a large amount of white precipitate or viscous oily matter, and filtering and separating out solid or oily matter, namely RTTCA-amino acid ester salt;

s40, washing the filtrate with 10mol/L NaOH and 50mol/L brine successively;

s50, drying the washed solution organic layer by a drying agent, evaporating to remove the solvent to obtain the optically active amino acid ester with the optical purity of 63 percent ~ 75 percent;

s60, adding 1.5moL/L NaOH solution into RTTCA-amino acid ester ammonium salt solution to decompose salt, extracting with ethyl acetate, and separating optically active amino acid ester with optical purity of 58% ~ 69%.

3. The method of claim 2, further comprising the steps of:

s70, adding dilute hydrochloric acid to the extracted liquid to adjust the pH =1, and extracting RTTCA with ethyl acetate.

4. The method of claim 3, wherein the RTTCA recovery is 81% ~ 85%.

5. The production method according to claim 1 or 2, characterized in that: the resolving agent is one of brominated camphor sulfonic acid, a-phenyl ethylamine and tartaric acid.

6. The production method according to claim 1 or 2, characterized in that: the drying agent described in S50 is anhydrous dry sodium sulfate, anhydrous calcium chloride or silica gel.

Technical Field

The invention relates to the technical field of amino acid, in particular to a preparation method of chiral amino acid ester.

Background

An amino acid is a compound in which a hydrogen atom on a carbon atom of a carboxylic acid is substituted with an amino group, and the amino acid molecule contains both amino and carboxyl functional groups. Amino acids, like hydroxy acids, can be classified as α -, β -, γ -, w-amino acids according to the position of the amino group attached to the carbon chain, but the amino acids obtained after proteolysis are all α -amino acids, and only twenty, which are the basic units constituting proteins.

Most chiral amino acid preparation methods in the market at present have low recovery rate and conversion rate, so that a chiral amino acid preparation method with high recovery rate and conversion rate is urgently needed.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides a preparation method of chiral amino acid ester, which has the advantages of high recovery rate and high conversion rate.

In order to realize the purpose of high recovery rate and conversion rate, the invention provides the following technical scheme: a preparation method of chiral amino acid ester is a chemical resolution method, and the chemical resolution method comprises the following steps:

s10, dissolving DL-amino acid ester in ethyl acetate;

s20, taking a resolving agent to carry out chiral resolution on the DL amino acid ester solution;

s30, dripping an ethyl acetate solution containing RTTCA into the DL amino acid ester solution after chiral resolution, stirring for reaction for 30 ~ 60min, precipitating a large amount of white precipitate or viscous oily matter, and filtering to separate out solid or oily matter, namely RTTCA-amino acid ester salt 1 a;

s40, washing the filtrate with NaOH and saturated saline solution sequentially;

s50, drying the washed organic layer by a drying agent, evaporating to remove the solvent to obtain the optically active amino acid ester 2a with the optical purity of 63 percent ~ 75 percent;

s60, adding 6-12 parts of RTTCA-amino acid ester salt 1a solution into NaOH solution to decompose the salt.

S70, extracting with ethyl acetate to separate optically active amino acid ester 3a with optical purity of 58% ~ 69%.

As a specific implementation process, the method comprises the following processes:

s10, dissolving 2mmo1 parts of DL-amino acid ester in 10ml of ethyl acetate;

s20, taking a resolving agent to carry out chiral resolution on the DL amino acid ester solution;

s30, dripping 10ml of ethyl acetate solution containing 1mmol of RTTCA into the DL amino acid ester solution after chiral resolution, stirring and reacting for 30 ~ 60min, precipitating a large amount of white precipitate or viscous oily matter, and filtering and separating out solid or oily matter, namely RTTCA-amino acid ester salt 1 a;

s40, washing the filtrate by 10mol/L NaOH and 50mol/L saturated saline solution (3x5m 1);

s50, drying the washed solution organic layer by a drying agent, evaporating to remove the solvent to obtain the optically active amino acid ester 2a with the optical purity of 63 percent ~ 75 percent;

s60, adding 6-12 parts of RTTCA-amino acid ester salt 1a solution into 10ml of 1.5moL/LNaOH solution to decompose the salt;

s70, extracting with ethyl acetate (3x10m1) to separate optically active amino acid ester 3a with optical purity of 58% ~ 69%;

and S80, adding dilute hydrochloric acid into the extracted liquid to adjust the pH to be =1, extracting the liquid by using ethyl acetate to recover RTTCA, wherein the recovery rate is 81% and ~ 85% respectively.

The resolving agent can be one of brominated camphor sulfonic acid, a-phenyl ethylamine, tartaric acid and the like.

The desiccant in S50 is anhydrous sodium sulfate, anhydrous calcium chloride or silica gel

Compared with the prior art, the invention provides a preparation method of chiral amino acid, which has the following beneficial effects:

the yield of the prepared chiral amino acid ester reaches 60 percent, is 10 to 20 percent higher than that of the common method on the market, and the RTTCA can be recovered by extracting with ethyl acetate, the recovery rate is 82 percent ~ 85 percent, so that the resource is saved, and the pollution to the environment is reduced.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.