AR064949A1 - A PROCEDURE FOR PREGABALINE PREPARATION - Google Patents

A PROCEDURE FOR PREGABALINE PREPARATION

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Publication number
AR064949A1
AR064949A1 ARP080100219A AR064949A1 AR 064949 A1 AR064949 A1 AR 064949A1 AR P080100219 A ARP080100219 A AR P080100219A AR 064949 A1 AR064949 A1 AR 064949A1
Authority
AR
Argentina
Prior art keywords
methyl
acid
nitro
hexanoic acid
malonate
Prior art date
Application number
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Spanish (es)
Original Assignee
Enaltec Labs Pvt Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Enaltec Labs Pvt Ltd filed Critical Enaltec Labs Pvt Ltd
Priority to ARP080100219 priority Critical patent/AR064949A1/en
Publication of AR064949A1 publication Critical patent/AR064949A1/en

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Se provee un procedimiento para la preparacion de pregabalina, el cual comprende: (a) someter a una reaccion de Vilsmeier al compuesto 4-metil pentan-2-ona con oxicloruro de fosforo en presencia de dimetilformamida, para obtener 3-cloro-5-metil hex- 2-enal, (b) someter al 3-cloro- 5-metil hex-2-enal a una oxidacion con trioxido de cromo, para obtener el ácido 3-cloro-5-metil hex-2-enoico, (c) someter al ácido 3-cloro-5-metil hex-2-enoico a un acoplamiento de sonogashira con nitrometano, para obtener el ácido 5-metil-3-(nitro metil) hexenoico, (d) reducir el ácido 5-metil-3-(nitrometil) hexenoico con una reduccion catalítica leve, para obtener el ácido 5-metil-3-(nitrometil) hexenoico con una pureza enantiomérica mayor al 99,9%, (e) realizar la resolucion del ácido 5-metil-3-(nitro metil) hexanoico con un agente de resolucion, tal como una base auxiliar quiral, para obtener el ácido 3(S)-5-metil-3-(nitro metil) hexanoico y (f) reducir el ácido 3(S)-5-metil-3-(nitro metil) hexanoico para obtener el ácido 3(S)-5-metil-3-(amino metil) hexanoico, con una pureza enantiomérica mayor al 99,9%. También se provee un procedimiento para la preparacion de pregabalina, el cual comprende: (a) hacer reaccionar 3-Metil butanal con dietilmalonato en presencia de una base, para obtener dietil (3-metilbutiliden)malonato, (b) someter al dietil (3-etilbutiliden)malonato una reaccion de Michael con nitrometano, para obtener un dietil [3-metil-1-(nitrometil)butil] malonato, (c) someter a hidrolisis y a descarboxilacion al dietil [3-metil-1-(nitrometil)butil]malonato en presencia de una base fuerte en alcoholes primarios, para obtener el ácido 5-metil-3-(nitro metil) hexanoico, (d) resolver el ácido 5-metil-3-(nitro metil) hexanoico con un agente de resolucion tal como una base auxiliar quiral, para obtener el ácido 3(S)-3-(nitro metil)-5-metil hexanoico con una pureza enantiomérica mayor al 99,9% y (e) reducir el ácido 3(S)-3-(nitrometil)-5-metil hexanoico con reduccion catalítica, para obtener un ácido 3(S)-3-(aminometil)-5-metil hexanoico con una pureza enantiomérica mayor al 99,9%.A process for the preparation of pregabalin is provided, which comprises: (a) undergoing a Vilsmeier reaction to the 4-methyl pentan-2-one compound with phosphorus oxychloride in the presence of dimethylformamide, to obtain 3-chloro-5- methyl hex-2-enal, (b) subject 3-chloro-5-methyl hex-2-enal to oxidation with chromium trioxide, to obtain 3-chloro-5-methyl hex-2-enoic acid, ( c) subject 3-chloro-5-methyl hex-2-enoic acid to a coupling of sonogashira with nitromethane, to obtain 5-methyl-3- (nitro methyl) hexenoic acid, (d) reduce 5-methyl acid -3- (nitrometil) hexenoic acid with a slight catalytic reduction, to obtain 5-methyl-3- (nitrometyl) hexenoic acid with an enantiomeric purity greater than 99.9%, (e) perform the resolution of 5-methyl acid- 3- (nitro methyl) hexanoic acid with a resolving agent, such as a chiral auxiliary base, to obtain 3 (S) -5-methyl-3- (nitro methyl) hexanoic acid and (f) reduce acid 3 (S ) -5-methyl-3- (nitro methyl) hexa noic to obtain 3 (S) -5-methyl-3- (amino methyl) hexanoic acid, with an enantiomeric purity greater than 99.9%. A process for the preparation of pregabalin is also provided, which comprises: (a) reacting 3-Methyl butanal with diethylmalonate in the presence of a base, to obtain diethyl (3-methylbutylidene) malonate, (b) subject to diethyl (3 -ethylbutylidene) malonate a reaction of Michael with nitromethane, to obtain a diethyl [3-methyl-1- (nitromethyl) butyl] malonate, (c) subject to hydrolysis and decarboxylation to diethyl [3-methyl-1- (nitromethyl) butyl ] malonate in the presence of a strong base in primary alcohols, to obtain 5-methyl-3- (nitro methyl) hexanoic acid, (d) solve 5-methyl-3- (nitro methyl) hexanoic acid with a resolving agent such as a chiral auxiliary base, to obtain 3 (S) -3- (nitro methyl) -5-methyl hexanoic acid with an enantiomeric purity greater than 99.9% and (e) reduce acid 3 (S) -3 - (nitrometil) -5-methyl hexanoic acid with catalytic reduction, to obtain a 3 (S) -3- (aminomethyl) -5-methyl hexanoic acid with an enantiomeric purity greater than 99, 9%

ARP080100219 2008-01-17 2008-01-17 A PROCEDURE FOR PREGABALINE PREPARATION AR064949A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
ARP080100219 AR064949A1 (en) 2008-01-17 2008-01-17 A PROCEDURE FOR PREGABALINE PREPARATION

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ARP080100219 AR064949A1 (en) 2008-01-17 2008-01-17 A PROCEDURE FOR PREGABALINE PREPARATION

Publications (1)

Publication Number Publication Date
AR064949A1 true AR064949A1 (en) 2009-05-06

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Family Applications (1)

Application Number Title Priority Date Filing Date
ARP080100219 AR064949A1 (en) 2008-01-17 2008-01-17 A PROCEDURE FOR PREGABALINE PREPARATION

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AR (1) AR064949A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9745249B2 (en) 2014-06-12 2017-08-29 Siegfried Ltd. Method for the preparation of beta-substituted gamma-amino carboxylic acids

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9745249B2 (en) 2014-06-12 2017-08-29 Siegfried Ltd. Method for the preparation of beta-substituted gamma-amino carboxylic acids

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