Preparation method of 2-alkyl-2-aminopropionate hydrochloride

An aminopropionate, hydrochloride technology, applied in the preparation of organic compounds, chemical instruments and methods, cyanide reaction preparation and other directions, can solve the problems of high cost, incomplete reaction of raw materials, high price of BOC acid anhydride, etc. The effect of high product yield and low price

Pending Publication Date: 2020-07-10
安徽红杉生物医药科技有限公司
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  • Abstract
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  • Claims
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Problems solved by technology

[0003] In the prior art, in the synthesis process of 2-alkyl-2-aminopropionate hydrochloride, since the amino group of L-alanine is prone to amidation reaction in the esterification reaction, the following two paths are usually used Synthesis: one is to use BOC anhydride to protect the amino group of L-alanine before the esterification reaction, but the price of BOC anhydride is expensive, resulting in high synthesis costs; the other is to carry out esterification under the condition of thionyl chloride , using thionyl chloride to hydrochloride the amino group of L-alanine, but the research found that the reaction of the raw materials in this synthetic route is not complete, and the molar yield of the product can only reach about 60% usually

Method used

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  • Preparation method of 2-alkyl-2-aminopropionate hydrochloride
  • Preparation method of 2-alkyl-2-aminopropionate hydrochloride
  • Preparation method of 2-alkyl-2-aminopropionate hydrochloride

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preparation example Construction

[0014] The embodiment of the present application provides a preparation method of 2-alkyl-2-aminopropionate hydrochloride, which includes: mixing L-alanine and alkyl alcohol at a temperature of -10 to 5°C Add thionyl chloride dropwise into the solution, heat preservation treatment to hydrochloride the amino group of L-alanine to obtain a reaction stock solution. The reaction stock solution is heated to 75-85°C in the presence of molecular sieves to carry out esterification reaction to obtain a reaction solution containing 2-alkyl-2-aminopropionate hydrochloride.

[0015] In the examples of this application, the amino group of L-alanine was hydrochloridized first by using thionyl chloride, and the esterification reaction during hydrochlorication was avoided under the temperature condition of -10~5°C, effectively avoiding the occurrence of L-alanine The amino group of the amino acid undergoes an amidation reaction in the esterification reaction, and there is no need to use BOC a...

Embodiment 1

[0036] A preparation method of (S)-2-ethylbutyl-2-aminopropionate hydrochloride, comprising:

[0037] S1. Add 100g of L-alanine to 450mL of 2-ethyl-1-butanol, lower the temperature of the system to below 0°C, and drop 160g of thionyl chloride into the mixture. During the dropwise addition, the temperature of the system was controlled below 5°C, and after the dropwise addition was completed, the temperature was kept below 5°C for 30 minutes to obtain the reaction stock solution.

[0038] S2. Add 4A molecular sieve to the reaction stock solution, the mass ratio of 2-ethyl-1-butanol to 4A molecular sieve is 1:0.05; then heat the reaction stock solution to 80°C for 10h to obtain (S)-2-Ethyl The reaction solution of butyl-2-aminopropionate hydrochloride.

[0039] S3. Filter the reaction solution to remove the molecular sieve, then concentrate the reaction solution to a slurry, add 100mL petroleum ether to crystallize, filter and dry the crystal, (S)-2-ethylbutyl-2-aminopropionate ...

Embodiment 2

[0041] A preparation method of (S)-2-ethylbutyl-2-aminopropionate hydrochloride, comprising:

[0042] S1. Add 100g of L-alanine to 450mL of 2-ethyl-1-butanol, lower the temperature of the system to below 0°C, and drop 160g of thionyl chloride into the mixture. During the dropwise addition, the temperature of the system was controlled below 5°C, and after the dropwise addition was completed, the temperature was kept below 5°C for 30 minutes to obtain the reaction stock solution.

[0043] S2. Add 3A molecular sieve to the reaction stock solution, the mass ratio of 2-ethyl-1-butanol to 3A molecular sieve is 1:0.05; then heat the reaction stock solution to 80°C for 10h to obtain (S)-2-ethyl The reaction solution of butyl-2-aminopropionate hydrochloride.

[0044] S3. Filter the reaction solution to remove the molecular sieve, then concentrate the reaction solution to a slurry, add 100mL petroleum ether to crystallize, filter and dry the crystal to obtain (S)-2-ethylbutyl-2-aminopr...

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Abstract

The invention provides a preparation method of 2-alkyl-2-aminopropionate hydrochloride, and belongs to the technical field of synthesis of medical intermediates. The preparation method of the 2-alkyl-2-aminopropionate hydrochloride comprises the following steps: adding thionyl chloride into a mixed solution of L-alanine and alkyl alcohol dropwise at a temperature ranging from -10DEG C to 5DEG C, and carrying out heat preservation treatment for hydrochlorination of the amino of L-alanine to obtain a reaction stock solution; and heating the reaction stock solution to 75-85DEG C in the presence of a molecular sieve, and carrying out esterification reaction to obtain a reaction solution containing 2-alkyl-2-aminopropionate hydrochloride. In the preparation method, the price of the raw materials is low and the yield of the product is high.

Description

technical field [0001] The application relates to the technical field of synthesis of pharmaceutical intermediates, in particular, to a preparation method of 2-alkyl-2-aminopropionate hydrochloride. Background technique [0002] 2-Alkyl-2-aminopropionate hydrochloride is a commonly used pharmaceutical intermediate, wherein (S) 2-ethylbutyl-2-aminopropionate hydrochloride can be used to synthesize antiviral The pharmaceutical intermediate of the drug remdesivir has important application value. [0003] In the prior art, in the synthesis process of 2-alkyl-2-aminopropionate hydrochloride, since the amino group of L-alanine is prone to amidation reaction in the esterification reaction, the following two paths are usually used Synthesis: one is to use BOC anhydride to protect the amino group of L-alanine before the esterification reaction, but the price of BOC anhydride is expensive, resulting in high synthesis costs; the other is to carry out esterification under the condition...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C227/18C07C229/08
CPCC07C227/18C07C229/08
Inventor 高仰哲吴法浩李钢王志航
Owner 安徽红杉生物医药科技有限公司
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