WO2020031201A1 - Procédé amélioré pour la préparation de l'acide 6-aminohexanoïque - Google Patents

Procédé amélioré pour la préparation de l'acide 6-aminohexanoïque Download PDF

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Publication number
WO2020031201A1
WO2020031201A1 PCT/IN2019/050572 IN2019050572W WO2020031201A1 WO 2020031201 A1 WO2020031201 A1 WO 2020031201A1 IN 2019050572 W IN2019050572 W IN 2019050572W WO 2020031201 A1 WO2020031201 A1 WO 2020031201A1
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Prior art keywords
acid
solvent
solvents
formula
aminohexanoic acid
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Ceased
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PCT/IN2019/050572
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English (en)
Inventor
Thirumalai Rajan Srinivasan
Eswaraiah Sajja
Rajeshwar Reddy Sagyam
Navin Kumar Reddy KESHAVAREDDY
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MSN Laboratories Pvt Ltd
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MSN Laboratories Pvt Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
    • 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
    • C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
    • 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
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives
    • C07C227/40—Separation; Purification
    • C07C227/42—Crystallisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D223/08—Oxygen atoms
    • C07D223/10—Oxygen atoms attached in position 2

Definitions

  • the present invention relates to highly pure 6-aminohexanoic acid of formula- 1 and process for its preparation thereof.
  • the present invention also relates to an improved process for the preparation of caprolactam of formula-2 which is used for the preparation of 6-aminohexanoic acid of formula- 1.
  • 6-Aminohexanoic acid is also known as aminocaproic acid, epsilon-aminocaproic acid or e-aminocaproic acid. 6-Aminohexanoic acid is acts as an inhibitor of fibrinolysis which is approved with the brand name of AMICAR ® with different dosage forms such as 500mg and lgm as a tablet, l.25gm/5ml as a syrup and 250mg/ml as an injectable injection. It is useful in enhancing hemostasis when fibrinolysis contributes to bleeding. Fibrinolytic bleeding may frequently be associated with surgical complications following heart surgery (with or without cardiac bypass procedures) and portacaval shunt, hematological disorders and neoplastic diseases.
  • US patent document 7491520 B2 discloses a biochemical synthesis of 6- aminohexanoic acid from 6-aminohex-2-enoic acid using an enzymes having a,b-enoate reductase activity such as Acremonium strictum, Clostridium tyrobutyricum, Moorella thermoacetica, Ochrobactrum anthropi, or Clostridium kluyveri.
  • an enzymes having a,b-enoate reductase activity such as Acremonium strictum, Clostridium tyrobutyricum, Moorella thermoacetica, Ochrobactrum anthropi, or Clostridium kluyveri.
  • US patent document 8404465 B2 discloses a process for the preparation of 6- aminohexanoic acid from Lysine using a microoganisam includes at least one nucleic acid encoding a polypeptide by catalyzation and the said process is schematically shown as follows:
  • US patent document 9663805 B2 discloses a process for the preparation of 6- aminohexanoic acid from a-ketopimelic acid using a bio-catalyst comprising of two enzymes.
  • US patent document 8809581 B2 discloses a process for the preparation of 6- aminohexanoic acid comprising reaction of caprolactam with sodium hydroxide or potassium hydroxide and a solubility regulating agent to form an intermediate compound which is hydrogenated in presence of Pd(OH) 2 catalyst to produce 6-aminohexanoic acid.
  • US patent document 9776953 B2 discloses a process for the preparation of 6- aminohexanoic acid comprising hydrolysis of caprolactam with hydrochloride and then tedious work up/azeotropic distillation with toluene followed by isolation/purification from isopropanol to get pure protic acid salts of 6-aminohexanoic acid which is further treating with an organic base in methanol followed by final purification from methanol, acetone in presence of seeds of 6-aminohexanoic acid.
  • 6-Aminohexanoic acid has a maximum daily dose of about 24 gm.
  • EMA and other regulatory agencies issues guidelines to limit the chemical impurities, inorganic impurities, organic volatile solvents and other impurities in 6-aminohexanoic acid drug substance as much as possible.
  • the present invention provides highly pure 6-aminohexanoic acid of formula- 1 which is free of organic volatile impurities like n-pentane, cyclohexane, n- heptane, isopropanol, pentanol, benzene..
  • the present invention provides highly pure 6-aminohexanoic acid of formula- 1 substantially free of caprolactam impurity.
  • the present invention provides highly pure 6-aminohexanoic acid of formula- 1 which is free of chloride impurity.
  • the present invention provides an improved process for the preparation of 6-aminohexanoic acid of formula- 1.
  • the present invention provides an improved process for the preparation of highly pure 6-aminohexanoic acid of formula- 1.
  • the present invention provides an improved a process for the preparation of caprolactam of formula-2.
  • Figure- 1 Illustrates the Powdered X-Ray Diffraction (PXRD) Pattern of crystalline form of 6-aminohexanoic acid obtained according to example-3.
  • PXRD Powdered X-Ray Diffraction
  • Figure-2 Illustrates the Powdered X-Ray Diffraction (PXRD) Pattern of crystalline form of 6-aminohexanoic acid obtained according to example-6.
  • PXRD Powdered X-Ray Diffraction
  • suitable solvent refers to “hydrocarbon solvents” such as n-hexane, n-heptane, cyclohexane, pet ether, benzene, toluene, pentane, cycloheptane, methyl cyclohexane, ethylbenzene, m-, o-, or p-xylene, or naphthalene and the like;“ether solvents” such as dimethoxymethane, tetrahydrofuran, 1,3- dioxane, l,4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, 1 ,2-dimethoxy ethanethane, 1,3- dioxane,
  • suitable base refers to inorganic bases like“alkali metal carbonates” such as sodium carbonate, potassium carbonate, lithium carbonate and the like; “alkali metal bicarbonates” such as sodium bicarbonate, potassium bicarbonate and the like; “alkali metal hydroxides” such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like; alkali metal hydrides such as sodium hydride, potassium hydride, lithium hydride and the like; alkali metal amides such as sodium amide, potassium amide, lithium amide or mixtures thereof.
  • suitable acid refers to acid such as formic acid, acetic acid, oxalic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, methanesulfonic acid, / oluenesulfonic acid and the like.
  • the term“highly pure” refers to 6-aminohexanoic acid contains purity greater than about 99.90% by high performance liquid chromatography (HPLC) or greater than about 99.95% by HPLC or greater than about 99.98% by HPLC or greater than about 99.99% by HPLC.
  • the term“substantially free” in related to chemical compound as impurity refers to a content of less than about 0.05% or less than about 0.04% or less than about 0.03% or less than about 0.02% or less than about 0.01% or absent.
  • Free of chloride content herein refers to less than about 0.05% or absent.
  • the term“free” refers to 6-aminohexanoic acid contains less than 2000 ppm or 1000 ppm or 500 ppm or 100 ppm or 50 ppm or absent of organic volatile impurities such as n-pentane, cyclohexane, n-heptane, isopropanol, pentanol, benzene and the like.
  • the chemical compound as impurity is measured by high performance liquid chromatography (HPLC), organic volatile impurity is measured by gas chromatography (GC) and chloride content is measured by ion chromatography (IC).
  • HPLC high performance liquid chromatography
  • GC gas chromatography
  • IC ion chromatography
  • the present invention provides highly pure 6-aminohexanoic acid of formula- 1 which is free of organic volatile impurities.
  • first embodiment provides highly pure 6-aminohexanoic acid of formula- 1 contains isopropanol organic volatile impurity less than about 1100 ppm.
  • the present invention provides highly pure 6-aminohexanoic acid of formula- 1 substantially free of caprolactam impurity.
  • the present invention provides highly pure 6-aminohexanoic acid of formula- 1 free of chloride content.
  • the present invention provides an improved process for the preparation of 6-aminohexanoic acid of formula-l, comprising:
  • the inorganic base is selected form“alkali metal hydroxides” such as sodium hydroxide, potassium hydroxide and the like; alkali metal carbonates” such as sodium carbonate, potassium carbonate, lithium carbonate and the like;“alkali metal bicarbonates” such as sodium bicarbonate, potassium bicarbonate and the like; prefarebly alkali metal hydroxides;
  • the solvent is polar protic solvent selected from water or alcohol solvents such as methanol, ethanol, n-propanol or isopropanol or mixtures thereof; prefarebly water;
  • the acid is selected from acetic acid, formic acid, propanoic acid, oxalic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and the like; prefarebly acetic acid;
  • the suitable organic solvent is selected from alcohol solvents, hydrocarbon solvents, ether solvents, chloro solvents, ketone solvents
  • the present invention provides an improved process for the preparation of 6-aminohexanoic acid of formula-l, comprising: a) reacting the caprolactam with aqueous potassium hydroxide solution,
  • step-b filtering the mixture obtained in step-b), d) neutralizing the filtrate obtained in step-c) with acetic acid to provide 6- aminohexanoic acid.
  • the present invention provides an improved process for the preparation of highly pure 6-aminohexanoic acid, comprising:
  • step-a) or step-b) combining the filtrate obtained in step-a) or step-b) with anti-solvent to provide highly pure 6-aminohexanoic acid.
  • step-a) the suitable organic solvent is same as defined hereinbefore; in step-a) the temperature is ranging from 25 °C to reflux temperature of the solvent used; in step-c), the anti-solvent is selected from methanol, ethanol, isopropanol, n-propanol, n-butanol, chloroform and the like.
  • the present invention provides 6- aminohexanoic acid of formula- 1 having purity greater than about 99.90% by high performance liquid chromatography (HPLC). Prefarebly, about 99.98% by HPLC.
  • the present invention provides a process for the preparation of caprolactam of formula-2, comprising:
  • step-a) reacting the cyclohexanone with hydroxylamine or its salt in a suitable solvent, b) in-situ treating the product obtained in step-a) with suitable acid to provide caprolactam of formula-2.
  • the hydroxylamine salt is selected from sulfate, hydrochloride, hydrobromide, hydroiodide and the like;
  • the suitable solvent is selected from hydrocarbon solvents, ether solvents, chloro solvents, ketone solvents, nitrile solvents, alcohol solvents, polar solvents or mixtures thereof;
  • the acid is mineral acid such as sulfuric acid, nitric acid and the like or organic acid such as formic acid, acetic acid, methanesulfonic acid, p-toluenesulfonic acid, camphor sulfonic acid and the like.
  • the caprolactam obtained by the present invention can be isolated by crystallization or recrystallization from the solvent wherein, the solvent is selected from hydrocarbon solvents, ether solvents, chloro solvents, ketone solvents, nitrile solvents, alcohol solvents, polar solvents or mixtures thereof, and/or the isolation also carried out by the methods like distillation, decantation, filtration and then drying any other methods known in the art.
  • the solvent is selected from hydrocarbon solvents, ether solvents, chloro solvents, ketone solvents, nitrile solvents, alcohol solvents, polar solvents or mixtures thereof, and/or the isolation also carried out by the methods like distillation, decantation, filtration and then drying any other methods known in the art.
  • the present invention provides pharmaceutical compositions comprising highly pure aminohexanoic acid of formula (1) and pharmaceutically acceptable excipient.
  • composition comprising highly pure aminohexanoic acid of formula (1) and pharmaceutically acceptable excipient is formulated in a manner suitable for the route of administration to be used.
  • compositions include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, or injection preparations.
  • a liquid chromatographic system is equipped with variable wavelength UV detector; Column: Inertsil ODS-3V 250*4.6 mm, 5pm (or) equivalent; Column temperature: 40°C; Wave length: 210 nm; Injection volume: 20.0 pL; Elution: isocratic; Diluent: Milli-Q- water; Solution-A: weigh accurately about 0.55gr of sodium l-heptanesulfonate and transfer into 600 mL of diluent.
  • Mobile phase Dissolve lOgr of monobasic potassium phosphate in 300 ml of solution-A and added 250 mL of methanol. H3PO4 was added to the mixture to adjust to a pH of 2.2 and diluted with Solution-A.
  • Caprolactam obtained by the process of the present invention is analyzed by Gas Chromatography (GC) under the following conditions:
  • a gas chromatographic system is equipped with FID; Column: DB-5 Capillary column (or) equivalent; Length: 30 mts; ID: 0.53 mm; film thickness: 3.0mih; Injector temperature: l80°C; split ratio: 1 :7; Injection volume: 0.0 pL; Diluent: methanol; Carrier gas: helium; hydrogen flow: 40 ml/min; air flow: 400 ml/min.
  • a mixture of cyclohexanone (100 gms), cyclohexane (100 ml) and hydroxylamine sulfate (100.35 gms) were stirred for 2 hrs at 25-30°C. Heated the reaction mixture to 45- 50°C and added sulfuric acid (254 gms) and then stirred for 2 hours at same temperature. Heated the reaction mixture to 75-80°C and stirred for 12 hrs at same temperature. Basified the reaction mixture with aqueous sodium hydroxide solution at l0-l5°C. n-Butanol (300 ml) was added to the above reaction mixture at 25-30°C and stirred for 15 min.
  • Caprolactam (100 gms) was added to freshly prepared aqueous potassium hydroxide solution (56.5 gms of potassium hydroxide dissolved in 90 ml of water) at 25-30°C. Heated the reaction mixture to 90-95°C and stirred for 10 hrs at same temperature. Isopropanol (600 ml) and charcoal (5 gms) were added to the reaction mixture at 25-30°C and stirred for 30 min at same temperature. Filtered the reaction mixture through hy-flow bed and washed with isopropanol. The obtained filtrate again filtered through filter paper and washed with isopropanol. Acetic acid (85 ml) was added to the above obtained filtrate to neutralized the pH at 25-30°C. Cooled the reaction mixture to 0-5°C and stirred for 3 hrs. Filtered the precipitated solid and then dried under reduced pressure.
  • the above obtained solid compound was added to water (94.5 ml) and isopropanol (220.5 ml) at 25-30°C and stirred for 10 min at same temperature. Heated the reaction mixture to 65-70°C and stirred for 30 min. Filtered the obtained solution through filter paper and washed with isopropanol. Isopropanol (504 ml) was added to the above filtrate at 25- 30°C and stirred for 8 hrs at same temperature. Filtered the precipitated solid, washed with isopropanol and then dried to afford the title compound.
  • Example-4 Process for the preparation of highly pure 6-aminohexanoic acid
  • Caprolactam (110 gms) was added to freshly prepared aqueous potassium hydroxide solution (62 gms of potassium hydroxide dissolved in 100 ml of water) at 25-30°C. Heated the reaction mixture to 90-95°C and stirred for 10 hrs at same temperature. Isopropanol (550 ml) and charcoal (5.5 gms) were added to the reaction mixture at 25-30°C and stirred for 30 min at same temperature. Filtered the reaction mixture through hy-flow bed and washed with isopropanol. Charcoal (5.5 gms) was added to the above obtained filtrate at 25-30°C and filtered for particle free solution, washed with isopropanol.
  • Example-5 Process for the preparation of pure 6-aminohexanoic acid
  • Caprolactam (500 gms) was added to freshly prepared aqueous potassium hydroxide solution (280 gms of potassium hydroxide dissolved in 450 ml of water) at 25-30°C. Heated the reaction mixture to 90-95°C and stirred for 10 hrs at same temperature. Isopropanol (2.5 Lt) and charcoal (25 gms) were added to the reaction mixture at 25-30°C and stirred for 30 min at same temperature. Filtered the reaction mixture through hy-flow bed and washed with isopropanol. Mixture of acetic acid (425 ml) and isopropanol (500 ml) solution was added to the obtained filtrate to neutralized the pH.
  • Example-6 Process for the preparation of highly pure 6-aminohexanoic acid
  • 6-Aminohexanoic acid 250 gms of example-5 was added to water (375 ml) and isopropanol (875 ml) at 25-30°C and stirred for 10 min. Heated the mixture to 65-70°C and stirred for 30 min. Filtered the obtained mixture and washed with isopropanol. Isopropanol (2000 ml) was added to obtained material and stirred for 8 hrs, filtered the compound and washed with isopropanol. The obtained wet compound was dried at 60-65°C under vacuum for 18 hrs and cooled to 25-30°C and then milled to afford the title compound.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne l'acide 6-aminohexanoïque très pur de formule 1 qui est exempt d'impuretés volatiles organiques, d'impureté caprolactame et un procédé amélioré pour sa préparation. La présente invention concerne également un procédé amélioré pour la préparation de caprolactame de formule 2 utilisé dans la préparation de l'acide 6-aminohexanoïque de formule 1.
PCT/IN2019/050572 2018-08-04 2019-08-03 Procédé amélioré pour la préparation de l'acide 6-aminohexanoïque Ceased WO2020031201A1 (fr)

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IN201841029394 2018-08-04
IN201841029394 2018-08-04

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111233704A (zh) * 2020-03-16 2020-06-05 湖北三宁碳磷基新材料产业技术研究院有限公司 一种制备6-氨基己腈产品的方法
CN111635330A (zh) * 2020-06-24 2020-09-08 江苏扬农化工集团有限公司 一种己二胺关键中间体反应残渣回收利用并联产羧酸的方法
CN114195663A (zh) * 2021-12-20 2022-03-18 昌德新材科技股份有限公司 一种6-氨基己酸的制备方法
CN114478283A (zh) * 2020-11-13 2022-05-13 珠海联邦制药股份有限公司 一种6-氨基己酸的制备方法
CN116041195A (zh) * 2022-12-23 2023-05-02 蚌埠丰原医药科技发展有限公司 一种赖氨酸线状二聚体的制备方法
CN116554043A (zh) * 2023-05-05 2023-08-08 常州兰陵制药有限公司 合成6-氨基己酸的2-(2-氨基乙基)环丁烷-1-酮的制备方法
CN116554045A (zh) * 2023-05-05 2023-08-08 常州兰陵制药有限公司 一种以环己酮一步合成制备6-氨基己酸的方法
CN116836073A (zh) * 2023-05-05 2023-10-03 常州兰陵制药有限公司 一种以庚二酸为原料制备6-氨基己酸的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1256899A (fr) * 1982-08-20 1989-07-04 Alexis Cordi Derives d'acides w-amino, preparation et utilisation desdits derives et composes les contenant
WO1997010197A1 (fr) * 1995-09-11 1997-03-20 Emisphere Technologies, Inc. PROCEDE POUR PREPARER DES DERIVES D'ACIDES φ-AMINOALCANOIQUES A PARTIR DE CYCLOALCANONES
US5900482A (en) * 1995-07-20 1999-05-04 Mitsubishi Chemical Corporation Process for the preparation of ε-caprolactam
US8809581B2 (en) * 2012-08-03 2014-08-19 Sunny Pharmtech Inc. Method of making 6-aminocaproic acid as active pharmaceutical ingredient
US20170036991A1 (en) * 2015-08-06 2017-02-09 Dipharma Francis S.R.L. Isolation and purification of 6-aminocaproic acid

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1256899A (fr) * 1982-08-20 1989-07-04 Alexis Cordi Derives d'acides w-amino, preparation et utilisation desdits derives et composes les contenant
US5900482A (en) * 1995-07-20 1999-05-04 Mitsubishi Chemical Corporation Process for the preparation of ε-caprolactam
WO1997010197A1 (fr) * 1995-09-11 1997-03-20 Emisphere Technologies, Inc. PROCEDE POUR PREPARER DES DERIVES D'ACIDES φ-AMINOALCANOIQUES A PARTIR DE CYCLOALCANONES
US8809581B2 (en) * 2012-08-03 2014-08-19 Sunny Pharmtech Inc. Method of making 6-aminocaproic acid as active pharmaceutical ingredient
US20170036991A1 (en) * 2015-08-06 2017-02-09 Dipharma Francis S.R.L. Isolation and purification of 6-aminocaproic acid

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DOLEZAL, P. ET AL.: "AMINOCAPROIC ACID ESTERS AS TRANSDERMAL PENETRATION ENHANCING AGENTS", PHARMACEUTICAL, 1993, XP055685295 *
GALAT, A. ET AL.: "THE PREPARATION OF -AMINOCAPROIC ACID", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 68, no. 12, 1946, pages 2729 - 2730 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111233704A (zh) * 2020-03-16 2020-06-05 湖北三宁碳磷基新材料产业技术研究院有限公司 一种制备6-氨基己腈产品的方法
CN111635330A (zh) * 2020-06-24 2020-09-08 江苏扬农化工集团有限公司 一种己二胺关键中间体反应残渣回收利用并联产羧酸的方法
CN111635330B (zh) * 2020-06-24 2023-01-24 江苏扬农化工集团有限公司 一种己二胺关键中间体反应残渣回收利用并联产羧酸的方法
CN114478283A (zh) * 2020-11-13 2022-05-13 珠海联邦制药股份有限公司 一种6-氨基己酸的制备方法
CN114478283B (zh) * 2020-11-13 2024-04-16 珠海联邦制药股份有限公司 一种6-氨基己酸的制备方法
CN114195663A (zh) * 2021-12-20 2022-03-18 昌德新材科技股份有限公司 一种6-氨基己酸的制备方法
CN116041195A (zh) * 2022-12-23 2023-05-02 蚌埠丰原医药科技发展有限公司 一种赖氨酸线状二聚体的制备方法
CN116554043A (zh) * 2023-05-05 2023-08-08 常州兰陵制药有限公司 合成6-氨基己酸的2-(2-氨基乙基)环丁烷-1-酮的制备方法
CN116554045A (zh) * 2023-05-05 2023-08-08 常州兰陵制药有限公司 一种以环己酮一步合成制备6-氨基己酸的方法
CN116836073A (zh) * 2023-05-05 2023-10-03 常州兰陵制药有限公司 一种以庚二酸为原料制备6-氨基己酸的方法

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