Title of Invention	"A PROCESS FOR THE PRODUCTION OF SUBSTITUTED ACRYLIC ACID ESTERS OF THE GENERAL FORMULA II"
Abstract	The present invention relates to a process for the production of substituted acrylic acid esters of the general formula II: in which R denotes a linear or branched, saturated or unsaturated aliphatic C1.3 residue, R1 denotes hydrogen or a linear or branched, saturated aliphatic C1-6 residue and R denotes a linear or branched, saturated aliphatic C1-6 residue, or R andR together form a saturated hydrocarbon chain with the formation of a 3-8-membered cycloaliphatic ring, characterised in that a ketone or an aldehyde of the general formula V, in which R and R have the above-stated meaning, is combined with trialkyl phosphonoacetate of the formula VI, in which R denotes a linear or branched, saturated or unsaturated aliphatic C1-3 group, and alkali metal carbonate as base in an aqueous solvent at a temperature in the range from 0 to 10°C and reacted at a temperature in the range of ≤ 25 °C.

Title of Invention

"A PROCESS FOR THE PRODUCTION OF SUBSTITUTED ACRYLIC ACID ESTERS OF THE GENERAL FORMULA II"

Abstract

The present invention relates to a process for the production of substituted acrylic acid esters of the general formula II: in which R denotes a linear or branched, saturated or unsaturated aliphatic C1.3 residue, R1 denotes hydrogen or a linear or branched, saturated aliphatic C1-6 residue and R denotes a linear or branched, saturated aliphatic C1-6 residue, or R andR together form a saturated hydrocarbon chain with the formation of a 3-8-membered cycloaliphatic ring, characterised in that a ketone or an aldehyde of the general formula V, in which R and R have the above-stated meaning, is combined with trialkyl phosphonoacetate of the formula VI, in which R denotes a linear or branched, saturated or unsaturated aliphatic C1-3 group, and alkali metal carbonate as base in an aqueous solvent at a temperature in the range from 0 to 10°C and reacted at a temperature in the range of ≤ 25 °C.

Full Text	The present invention relates to a process for the production of substituted acrylic acid esters of the general formula II. The present Invention relates to processes for the production of substituted acrylic acid esters and the use thereof to produce substituted γ-amino acids, such as gabapentin and pregabalin. Substituted γ-amino acids, such as gabapentin of formula (A) below and pregabalin of formula (B) below, are used as medicines for the treatment of epilepsy and pain (Formula Removed) A series of processes for the production of gabapentin and pregabalin are known from the prior art. Reference is made by way of example to a process described by J.S. Bryans et al. {J. Med. Chem. 41, 1838 -1845 (1998)) for the production of gabapentin. In accordance with this process, acrylic acid ethyl esters may be produced from ketones or aldehydes by Wadsworth-Eromons olefination with triethyl phosphonoacetate, in the presence of sodium hydride as base and in tetrahydrofuran WE CLAIM: 1. A process for the production of substituted acrylic acid esters of the general formula II: (Formula Removed) in which R denotes a linear or branched, saturated or unsaturated aliphatic C1-3 residue, R1 denotes hydrogen or a linear or branched, saturated aliphatic C1-6 residue and R denotes a linear or branched, saturated aliphatic C1-6 residue, or R1 and R2 together form a saturated hydrocarbon chain with the formation of a 3-8-membered cycloaliphatic ring, characterised in that a ketone or an aldehyde of the general formula V, in which R1 and R2 have the above-stated meaning, (Formula Removed) is combined with trialkyl phosphonoacetate of the formula VI, in which R denotes a linear or branched, saturated or unsaturated aliphatic C1-3 group, (Formula Removed) and alkali metal carbonate as base in an aqueous solvent at a temperature in the range from 0 to 10°C and reacted at a temperature in the range of ≤ 25 °C. 2. The process for the production of substituted acrylic acid esters of the general formula II, as claimed in claim 1 wherein R denotes a linear or branched, saturated or unsaturated aliphatic C1-3 residue, R1 denotes hydrogen or a linear or branched, saturated aliphatic C1-3 residue and R2 denotes a linear or branched, saturated aliphatic C1-4 residue, or R1 and R2 together form a saturated hydrocarbon chain with the formation of a 3-8-membered cycloaliphatic ring. 3. The process as claimed in claim 1 or 2, wherein a ketone or an aldehyde of the general formula V is reacted with trialkyl phosphonoacetate of the general formula VI, in which R denotes an ethyl group, in the presence of alkali metal carbonate, preferably potassium carbonate, in water. 4. The process as claimed in any one of claims 1 to 3, wherein, after the reaction, the substituted acrylic acid ester of the general formula II is purified by extraction. 5. The process as claimed in claim 4, wherein extraction is performed with diethyl ether. 6. A process as claimed in any one of claims 1 to 5, wherein cyclohexanone or 3-methylbutanal as a compound of the general formula V is reacted with triethyl phosphonoacetate as a compound of the general formula VI in each case to yield cyclohexylideneacetic acid ethyl ester or 5-methylhex-2-ene carboxylic acid ethyl ester respectively.

Full Text

The present invention relates to a process for the production of substituted acrylic acid esters of the general formula II.
The present Invention relates to processes for the production of substituted acrylic acid esters and the use thereof to produce substituted γ-amino acids, such as gabapentin and pregabalin.
Substituted γ-amino acids, such as gabapentin of formula (A) below and pregabalin of formula (B) below, are used as medicines for the treatment of epilepsy and pain (Formula Removed)
A series of processes for the production of gabapentin and pregabalin are known from the prior art. Reference is made by way of example to a process described by J.S. Bryans et al. {J. Med. Chem. 41, 1838 -1845 (1998)) for the production of gabapentin.
In accordance with this process, acrylic acid ethyl esters may be produced from ketones or aldehydes by Wadsworth-Eromons olefination with triethyl phosphonoacetate, in the presence of sodium hydride as base and in tetrahydrofuran

WE CLAIM:
1. A process for the production of substituted acrylic acid esters of the general formula II:
(Formula Removed)
in which R denotes a linear or branched, saturated or unsaturated aliphatic C1-3 residue,
R1 denotes hydrogen or a linear or branched, saturated aliphatic C1-6 residue and
R denotes a linear or branched, saturated aliphatic C1-6 residue, or
R1 and R2 together form a saturated hydrocarbon chain with the formation of a 3-8-membered
cycloaliphatic ring,
characterised in that
a ketone or an aldehyde of the general formula V, in which R1 and R2 have the above-stated
meaning,
(Formula Removed)
is combined with trialkyl phosphonoacetate of the formula VI, in which R denotes a linear or
branched,
saturated or unsaturated aliphatic C1-3 group,
(Formula Removed)
and alkali metal carbonate as base in an aqueous solvent at a temperature in the range from 0 to 10°C and reacted at a temperature in the range of ≤ 25 °C.

2. The process for the production of substituted acrylic acid esters of the general formula
II, as claimed in claim 1 wherein
R denotes a linear or branched, saturated or unsaturated aliphatic C1-3 residue,
R1 denotes hydrogen or a linear or branched, saturated aliphatic C1-3 residue and
R2 denotes a linear or branched, saturated aliphatic C1-4 residue, or
R1 and R2 together form a saturated hydrocarbon chain with the formation of a 3-8-membered
cycloaliphatic ring.
3. The process as claimed in claim 1 or 2, wherein a ketone or an aldehyde of the
general formula V is reacted with trialkyl phosphonoacetate of the general formula VI, in
which R denotes an ethyl group, in the presence of alkali metal carbonate, preferably
potassium carbonate, in water.
4. The process as claimed in any one of claims 1 to 3, wherein, after the reaction, the
substituted acrylic acid ester of the general formula II is purified by extraction.
5. The process as claimed in claim 4, wherein extraction is performed with diethyl ether.
6. A process as claimed in any one of claims 1 to 5,
wherein cyclohexanone or 3-methylbutanal as a compound of the general formula V is reacted with triethyl phosphonoacetate as a compound of the general formula VI in each case to yield cyclohexylideneacetic acid ethyl ester or 5-methylhex-2-ene carboxylic acid ethyl ester respectively.

Documents:

2109-delnp-2004-Abstract-(03-01-2011).pdf

2109-delnp-2004-Claims-(03-01-2011).pdf

2109-delnp-2004-Correspondence-Others-(03-01-2011).pdf

2109-delnp-2004-Description (Complete)-(03-01-2011).pdf

2109-delnp-2004-Form-1-(03-01-2011).pdf

2109-delnp-2004-Form-2-(03-01-2011).pdf

2109-delnp-2004-Form-3-(03-01-2011).pdf

2109-delnp-2004-GPA-(03-01-2011).pdf

2109-delnp-2004-Petition 137-(03-01-2011).pdf

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Patent Number

247922

Indian Patent Application Number

2109/DELNP/2004

PG Journal Number

23/2011

Publication Date

10-Jun-2011

Grant Date

03-Jun-2011

Date of Filing

21-Jul-2004

Name of Patentee

GRUNENTHAL GMBH

Applicant Address

ZIEGLERSTRASSE 6, D-52078, AACHEN, GERMANY

Inventors:

#	Inventor's Name	Inventor's Address
1	MICHAEL THOMAS PRZEWOSNY	SUERMONDTPLATZ 3, 52062 AACHEN, GERMANY
2	CLAUDIA PUTZ	HOLZSTR, 15,52349 DUREN, GERMANY

PCT International Classification Number

CO7C 67/343

PCT International Application Number

PCT/EP03/00213

PCT International Filing date

2003-01-11

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	102 03 122.3	2002-01-25	Germany