WO2021254235A1 - Procédé de synthèse de (s)-2-aminobutanamide - Google Patents

Procédé de synthèse de (s)-2-aminobutanamide Download PDF

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Publication number
WO2021254235A1
WO2021254235A1 PCT/CN2021/099297 CN2021099297W WO2021254235A1 WO 2021254235 A1 WO2021254235 A1 WO 2021254235A1 CN 2021099297 W CN2021099297 W CN 2021099297W WO 2021254235 A1 WO2021254235 A1 WO 2021254235A1
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WO
WIPO (PCT)
Prior art keywords
reaction
aminobutyrate
aminobutanamide
enzymatic hydrolysis
iii
Prior art date
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PCT/CN2021/099297
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English (en)
Chinese (zh)
Inventor
郑晨光
李敏勇
龚玉龙
朱元勋
颜峰峰
Original Assignee
浙江华海药业股份有限公司
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Application filed by 浙江华海药业股份有限公司 filed Critical 浙江华海药业股份有限公司
Priority to CN202180041077.1A priority Critical patent/CN115943137A/zh
Publication of WO2021254235A1 publication Critical patent/WO2021254235A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/30—Preparation of optical isomers
    • C07C227/34—Preparation of optical isomers by separation of optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/001—Amines; Imines
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
    • C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
    • 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

Definitions

  • the enzymatic hydrolysis reaction temperature in step (1) is 10-50°C, and the pH is 6.0-9.0.
  • the enzymatic hydrolysis reaction temperature is 25-40°C, and the pH is 6.5-8.0.
  • the reaction is stopped when the concentration of the isomer (R)-2-aminobutyrate relative to the reaction system is less than 1%, and the reaction time is 6-48 hours.
  • the desiccant used in the post-treatment of step (1) is preferably anhydrous magnesium sulfate or anhydrous sodium sulfate.
  • the distillation performed in the post-treatment of step (1) is preferably vacuum distillation, the temperature of the vacuum distillation is 20 to 100°C, preferably 40 to 70°C, and the pressure of the vacuum distillation is -0.05 to -0.1Mpa .
  • pressure values are all pressure values relative to standard atmospheric pressure, that is, the difference between absolute pressure and standard atmospheric pressure.
  • Aminolysis reaction add (S)-2-aminobutyric acid methyl ester (40g, 0.34mol) and methanol (120g) into the autoclave, stir and lower the temperature to -10°C, charge with NH3 to saturation, close the valve, and increase the temperature. To 25°C, control the temperature at 20 ⁇ 30°C, and keep the reactor pressure in the range of 0.3 ⁇ 0.5MPa for the reaction. TLC will track until the reaction is complete. After the ammonolysis reaction is over, collect the filtrate and evaporate the solvent under reduced pressure to obtain a solid. Dry to obtain (S)-2-aminobutanamide, yield 33.5g, yield 96.0%, HPLC purity 99.2%, isomer: 0.52%.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne un procédé de préparation (S)-2-aminobutanamide par un procédé enzymatique, comprenant l'utilisation de (R/S)-2-aminobutyrate en tant que matière première, le dédoublement de celle-ci sous l'action d'une hydrolase d'ester pour obtenir du (S)-2-aminobutyrate, et la mise en oeuvre supplémentaire d'une aminolyse pour obtenir du (S)-2-aminobutanamide. Le procédé présente une opération simple et une quantité moindre des trois déchets. De plus, le (S)-2-aminobutanamide obtenu par la réaction a une pureté élevée, satisfaisant ainsi aux exigences de production industrielle.
PCT/CN2021/099297 2020-06-19 2021-06-10 Procédé de synthèse de (s)-2-aminobutanamide WO2021254235A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202180041077.1A CN115943137A (zh) 2020-06-19 2021-06-10 一种(s)-2-氨基丁酰胺的合成方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010565694.9 2020-06-19
CN202010565694.9A CN113816872A (zh) 2020-06-19 2020-06-19 一种（s）-2-氨基丁酰胺的合成方法

Publications (1)

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WO2021254235A1 true WO2021254235A1 (fr) 2021-12-23

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Application Number Title Priority Date Filing Date
PCT/CN2021/099297 WO2021254235A1 (fr) 2020-06-19 2021-06-10 Procédé de synthèse de (s)-2-aminobutanamide

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CN (2) CN113816872A (fr)
WO (1) WO2021254235A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003014080A2 (fr) * 2001-08-10 2003-02-20 Ucb, S.A. Composes d'oxopyrrolidine, preparation de ces composes et utilisation de ceux-ci dans la fabrication de levetiracetam et d'analogues
CN101492382A (zh) * 2009-02-26 2009-07-29 绍兴新东泽化工有限公司 一种制备左乙拉西坦中间体s-(+)-2-氨基丁酸酯盐酸盐的新方法
CN101575300A (zh) * 2009-06-11 2009-11-11 绍兴文理学院 S-2-氨基丁酰胺的生产方法
CN105646265A (zh) * 2016-01-25 2016-06-08 江苏中邦制药有限公司 一种(s)-2-氨基丁酰胺的合成方法
CN106591179A (zh) * 2016-12-05 2017-04-26 长兴制药股份有限公司 甲基包囊菌及其在选择性拆分制备(S)‑α‑乙基‑2‑氧‑1‑吡咯烷乙酸盐上的应用
WO2019028671A1 (fr) * 2017-08-08 2019-02-14 浙江华海药业股份有限公司 Procédé de préparation de lévétiracétam
WO2019028666A1 (fr) * 2017-08-08 2019-02-14 浙江华海药业股份有限公司 Procédé de synthèse de lévétiracétam

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003014080A2 (fr) * 2001-08-10 2003-02-20 Ucb, S.A. Composes d'oxopyrrolidine, preparation de ces composes et utilisation de ceux-ci dans la fabrication de levetiracetam et d'analogues
CN101492382A (zh) * 2009-02-26 2009-07-29 绍兴新东泽化工有限公司 一种制备左乙拉西坦中间体s-(+)-2-氨基丁酸酯盐酸盐的新方法
CN101575300A (zh) * 2009-06-11 2009-11-11 绍兴文理学院 S-2-氨基丁酰胺的生产方法
CN105646265A (zh) * 2016-01-25 2016-06-08 江苏中邦制药有限公司 一种(s)-2-氨基丁酰胺的合成方法
CN106591179A (zh) * 2016-12-05 2017-04-26 长兴制药股份有限公司 甲基包囊菌及其在选择性拆分制备(S)‑α‑乙基‑2‑氧‑1‑吡咯烷乙酸盐上的应用
WO2019028671A1 (fr) * 2017-08-08 2019-02-14 浙江华海药业股份有限公司 Procédé de préparation de lévétiracétam
WO2019028666A1 (fr) * 2017-08-08 2019-02-14 浙江华海药业股份有限公司 Procédé de synthèse de lévétiracétam

Also Published As

Publication number Publication date
CN113816872A (zh) 2021-12-21
CN115943137A (zh) 2023-04-07

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