Title of Invention

A PROCESS FOR CONVERTING A TERTIARY OH GROUP OF AN ORGANIC COMPOUND INTO A TERTIARY CL GROUP OF THE ORGANIC COMPOUND.

Abstract Process for converting a tertiary OH group of an organic compound into a tertiary Cl group of the organic compound, characterized in that the tertiary alcohol is suspended or dissolved in a solvent selected from the group comprising toluene, o-xylene, m-xylene, p-xylene and mixtures thereof, thionyl chloride is added to the resultant suspension or solution, and the resultant organic compound comprising the tertiary Cl group is then separated from the further reaction components, the temperature range and/or the reaction time required is 35-45°C and 1 to 4 hours.
Full Text The present invention relates to a process for converting a tertiary OH group of an
organic compound into a tertiary Cl group of the organic compound.
In particular the invention relates to a process for producing a compound of general
formula (I)
and, more precisely, in the form of its racemates. its pure stereoisomers. in particular
enantiomers or diastereomers. or in the form of mixtures of stereoisomers. in
particular the enantiomers or diastereomers. in any mixing ratio; in the illustrated
form or in the form of its salts, in particular the physiologically acceptable salts,
particularly preferably in the form of the hydrochloride, or in the form of its
solvates. in particular the hydrates.
As is known EP 0 753 506 Al, the compound of formula (I) has an analgesic effect
and is also used as an intermediate product to produce further analgesic substances.
EP 0 753 506 Al discloses a process for producing the compound of formula (I)
starting from a compound of general formula (II).

the production of which is known from the literature (K. Flick et al., Arzneim.-
Forsch./Drug Res. 28 (1), issue la (1978)), wherein, to convert the tertiary alcohol
function on the cyclohexyl radical into a C-substitution with retention on the carbon
atom marked by *. thionyl chloride is used as the chlorination reagent and as the
solvent. This process therefore requires large quantities of thionyl chloride. The
subsequent working up while expelling the excess thionyl chloride with a stream of
nitrogen gas or by distillation is stressful for humans, the environment and operating
equipment. Furthermore, only poor yields (maximum of 55% of theoretical) are
achieved.
It is therefore an object of the invention to provide a process with which an organic
compound comprising a tertiary OH group, in particular a compound of formula (II).
is converted into a corresponding organic compound comprising a tertiary Cl group,
in particular into a compound of formula (I), in a high yield. It is also desirable to
reduce the quantity of chlorinating agent to be used, compared to the process known
from the literature, using this process.
The object is achieved by a process for converting a tertiary OH group of an organic
compound into a tertiary Cl group of the organic compound, characterised in that the
tertiary alcohol is suspended or dissolved in a solvent, selected from the group
comprising toluene, o-xylene. m-xylene, p-xylene and mixtures thereof, thionyl
chloride being added to the resultant suspension or solution and then the resultant
organic compound comprising the tertiary Cl group is separated from the further
reaction components.
It is preferred in this case that at least 1 equivalent but not more than 3 equivalents
of thionyl chloride is/are used. The preferred solvent is toluene.
Separation of the resultant organic compound comprising the tertiary Cl group can
be effected in different ways. Thus the organic compound comprising the tertiary Cl
group can be isolated, after the reaction has taken place, by distilling off the further
reaction components with the solvent. Distilling off is also taken to mean the partial
removal of the solvent with the further reaction components by supplying heat under
vacuum. It is also possible, after the reaction has taken place, to obtain the organic
compound comprising the tertiary Cl group as a solid by cooling to below ambient
temperature and to then dry it at temperatures between 35°C and 75°C, preferably
under vacuum. The halogenated organic compound is preferably obtained in the
form of its hydrochloride.
This process according to the invention allows synthesis of organic compounds
comprising a tertiary Cl group, starting from the corresponding tertiary alcohol
while retaining the stereochemistry at the stereogenic centre in high yields of more
than 70% and while reducing the quantity of thionyl chloride to be used.
The process according to the invention has proven to be particularly advantageous
for producing a compound of formula (I)
in the form of its racemates, its pure stereoisomers, in particular enantiomers or
diastereomers, or in the form of mixtures of stereoisomers, in particular the
enantiomers or diastereomers. in any mixing ratio; in the illustrated form or in the
form of its salts, in particular physiologically acceptable salts, particularly preferably
in the form of the hydrochloride, and/or in the form of its solvates, in particular the
hydrates; wherein the process is characterised in that a compound of formula (II)
in the form of its racemates. its pure stereoisomers. in particular enantiomers or
diastereomers. or in the form of mixtures of stereoisomers. in particular the
enantiomers or diastereomers. in any mixing ratio: in the illustrated form or in the
form of its salts, in particular physiologically acceptable salts, particularly preferably
in the form of the hydrochloride, and/or in the form of its solvates. in particular the
hydrates;
(a) is suspended in a solvent, which is selected from the group comprising
toluene, o-xylene, m-xylene, p-xylene and mixtures thereof;
(b) thionyl chloride is added to the resultant suspension; and
(c) the reaction product comprising the tertiary Cl group of formula (I) is
separated from the further reaction components.
It is advantageous here that the reaction product of formula (1) is separated (c) by
distilling off the solvent with the further reaction components. Distilling off is also
taken to mean the partial removal of the solvent with the further reaction
components by supplying heat under vacuum. Alternatively, separation (c) can take
place by precipitating the reaction product of formula (I) by means of cooling the
reaction mixture to below ambient temperature and then drying the reaction product
at temperatures between 35°C and 75°C, preferably under vacuum.
Toluene is preferred as the solvent or solubiliser. The use of other non-polar solvents
as toluene and/or xylene, for example THF, heptane, hexane and cyclohexane, has
not proven to be advantageous, as the reaction is then carried out with the formation
of numerous by-products, i.e. not sufficiently selectively. It is also preferred that 1 to
2 equivalents, in particular 1.5 to 1.7 equivalents, particularly preferably 1.6
equivalents of thionyl chloride - based on the compound of formula (II) - are used.
This represents a drastic reduction in the quantity of thionyl chloride to be used
compared with the process known from EP 0 753 506 Al. Much higher yields,
which are greater than 70% of the theoretical yield, are also achieved with complete
conversion of the starting compound (II).
The compound (II) is preferably reacted at elevated temperature, in particular at a
temperature of 30 to 50°C. preferably 35 to 45°C. for 1 to 4 hours, preferably 2 to 3
hours, though the reaction time can also be longer or shorter than this.
It has been found that the reaction according to the invention of (II) to (I) in the
presence of catalysts, for example dimethyl formamide. does not result in higher
conversion rates or improved yields; however, these catalysts do not disturb the
course of the reaction either.
The starting compound (II) is generally used in the form of its hydrochloride. It is
suspended in the inert or non-polar solubiliser, toluene, in which it does not dissolve
at either low or high temperature. The addition of the thionyl chloride, which for its
part is relatively non-polar, should not make any difference but during the course of
the reaction it will be seen that the educt (II) dissolves completely. It is also
surprising, and advantageous to process management as a whole, that - in contrast to
what is conventional in reactions with thionyl chloride, such as in the process of EP
0 753 506 A1 known from the literature, no sulphur dioxide gas and no hydrogen
chloride gas develops during heating. It is possible that the educt of formula (II)
and/or the product of formula (I) go into a complex comprising sulphur dioxide and
hydrogen chloride, so the compounds (I) and (II) remain in solution and SO2 and
HC1 are not released as gases. The complexing of amines with SO2 in organic
solvents is known in the literature (see for example J. Grundnes, S. D. Christian. J.
Am. Chem. Soc. (1968) 90. 2239-2245), while the - hypothetical - complexing with
HC1 has not previously been observed.
Irrespective of whether the hypothesis of complexing applies, the surprising
circumstance whereby the reactants of the reaction remain in a homogeneous
solution has proven to be advantageous with respect to yield and reaction. A further
advantage is that it is possible to separate the desired reaction product from the
solubiliser and the further reaction components in that the solubiliser. preferably
toluene, is distilled off. preferably under vacuum: the sulphur dioxide that has
formed and the hydrogen chloride are also removed in the process.
It is also advantageous to achieve separation of the product (I) by cooling the
reaction mixture to a temperature below ambient temperature, preferably to 0 to
10°C. in particular to about 2° bis 4°C. which leads to precipitation of the crude
product. Subsequent treatment in a drying cabinet at elevated temperatures of
preferably 35 to 75°C. in particular 40°C. and preferably under vacuum, in particular
at a pressure of 1 to 300 mbar, preferably 50 to 180 mbar, most particularly
preferably 50 to 150 mbar, yields the pure product, preferably as hydrochloride.
It is particularly preferred to carry out the process according to the invention with
the stereoisomers of compound (II) which have the configuration (IIa) and/or (IIb):
The reaction according to the invention with thionyl chloride leads, as expected with
retention of the stereochemistry at the centre of the reaction, to the corresponding
stereoisomers of compound (I). It is also preferred to use the compound (II) in the
process according to the invention as the enantiomer with the absolute configuration
(IIa). i.e. as (1S,2S)-2-dimethylaminomethyl-l-(3-methoxyphenyl)-cycIohexanol, in
particular as the hydrochloride. (1 S,2S)-[2-chloro-2-(3-methoxyphenyl)-
cyclohexylmethyl]-dimethylamine. in particular in the form of the HC1 salt, is
obtained as the product here.
As known from EP 753 506 Al. the compounds of formula (I) have an analgesic
effect and can be used as intermediate compounds to produce further analgesicalh
active cyclohexyl compounds.
It is therefore also preferred to convert a compound of formula (I), produced by the
process according to the invention by (d) catalytic hydrogenation. into a compound
of formula (III):
Hydrogenation is preferably carried out by heterogeneous catalysis with palladium
on activated carbon, of which the quantity can be varied within a wide range
between 1% through 5% to 10% palladium on activated carbon. Suitable solvents
include alkyl alcohols, in particular methanol and ethanol. The compound (I) is
conventionally used as the hydrochloride.
The hydrogenation step (d) is preferably carried out with retention of the
stereochemistry on the carbon atom marked by an asterisk (*) in formula (I) or (III).
The optionally formed quantity of compound (III) with inverted stereochemistry on
the carbon*atom is so low that it can easily be separated during conventional
working up. This process is therefore eminently suitable, starting from the
enantiomer with the absolute configuration (IIa), via the corresponding enantiomer
of compound (Ia)
for producing the compound (III) as the enantiomer with the absolute configuration
(IIIa)
(The compound (1Kb) mirror-inverted to (IIa) can be correspondingly produced,
starting from the optical antipode (IIb) via (Ib)).
As an alternative to hydrogenation by means of heterogeneous catalysis, the
compound of formula (III) is also accessible by hydrogenation with complex zinc-
boron hydrides of (I), as described in EP 0 753 506 Al.
The compound of formula (III), preferably produced by the process according to the
invention, can also be converted by methyl ether cleavage in a further step (e) into
the compound of formula (IV):
Aqueous hydrobromic acid was formerly used for this methyl ether cleavage (EP 0
753 506 Al). However, these reaction conditions have various drawbacks. To
achieve satisfactory yields therefore a high excess of acid has to be used, and. after
the reaction has taken place, has to be laboriously distilled off and destroyed. The
fact that methyl bromide is formed as the reaction product when HBr is used is
particularly serious. Methyl bromide is a toxic, highly flammable gas with a boiling
point of 4°C. which, it is suspected, damages the ozone layer of the earth's
atmosphere and for which a production ban in the European Union is therefore being
considered.
A process is therefore required which allows the desired methyl ether cleavage while
avoiding the use of HBr and at the same time guarantees high yields of the product
(IV).
It has accordingly been found that due to the simultaneous use of methionine and
methane sulphonic acid, the methyl ether cleavage of (III) to (IV) can be carried out
extremely easily and with high yields of more than 70%. (The use of
methionine/methane sulphonic acid to produce phenols has been described by N.
Fujii et al., J. Chem. Soc. Perkin I (1977) 2288-2298, but they do not convert any
amine-substituted compounds). Here the compound (III), preferably in the form of
the hydrochloride. is suspended in a mixture of a large excess of methane sulphonic
acid, conventionally between 5 and 40 equivalents, in particular 10 to 30
equivalents, particularly preferably about 20 equivalents, and 1 to 2. equivalents
preferably about 1.1 to 1.3 equivalents of methionine. and then heated for 1 to 12
hours, preferably 3 to 8 hours, in particular 5 hours, to temperatures of 50 to 100 °C.
preferably 70 to 90°C. After cooling and conventional working up. the desired
phenol (IV) is obtained in high yields without by-products and at most very small
quantities of unreacted starting material (III), preferably as hydrochloride: by
recrystallisation from water. (IV) is obtained in the form of hydrochloride hydrates.
It is surprising in this connection that the dimethylamino group otherwise very
unstable in an acid medium proves to be stable compared with the large excess of
methane sulphonic acid present.
An efficient process for producing the analgesic compound known from EP 0 753
506 Al with the absolute configuration (IVa), starting from the tertiary alcohol (II)
with the absolute configuration (IIa), is thus provided which can also be carried out
on an industrial scale. The synthesis sequence is shown in diagram I. (The same
applies to the optical antipode of (IVa) with (1S,2S) configuration.
Diagram 1
The invention will be described hereinafter by examples, without being limited
thereto.
Examples
The syntheses were carried out using commercially available reagents and
substances or with compounds that had been produced by processes known from the
literature.
The reaction products were identified and the chemical and optical purity analysed
by NMR spectroscopy and HPLC chromatography.
Example 1
Chlorination using thionyl chloride: Production of (lS,2S)-[2-chIoro-2-(3-
methoxy-phenyl)-cyclohexylmethyl]-dimethylamine hydrochloride
3 kg (10 mol) (1S.2S)-2-dimethylaminomethyl-l-(3-methoxy-phenyl)-cyclohexanol
hydrochloride were suspended in 10 1 toluene and heated to 30°C. 1.9 kg (16 mol)
thionyl chloride were added within 10 min. The mixture was heated to 35° to 45°C.
A clear solution was produced after 2 to 3 hours. Further processing was effected
according to variant A or B.
Variant A:
3 kg toluene were distilled off under vacuum via a gas washer. Hydrogen chloride
gas and sulphur dioxide escaped as the toluene was distilled off. The mixture was
then cooled to 2°C and stirred for 2 hours at this temperature. The precipitate was
centrifuged off and thoroughly rewashed with toluene. The product could be used
directly or after drying for subsequent hydrogenation. The yield was 2.87 kg (90 %
of theoretical) (1S,2S)-[2-chloro-2-(3-methoxyphenyl)-cyclohexylmethyl]-
dimethylamine hydrochloride.
Variant B:
The reaction mixture was cooled to 2°C and stirred for 4 hours. The precipitate
formed was centrifuged off and dried in a drying cabinet for 17 hours at 40°C and
under a vacuum of subsequent hydrogenation. The yield was 2.55 kg (80 % of theoretical) (lS,2S)-[2-
chloro-2-(3-methoxy-phenyl)-cyclohexylmethyl]-dimethylaminehydrochloride.
Identification was effected by comparing the analytical data of the product obtained
in variant A or B and the compound known from EP 0 753 506 Al, which exhibited
identity. The chemical and optical purity was analysed by HPLC on a Nucleosil 100-
5 C8 HD column (250 x 3 mm) by gradient elution with acetonitrile/water.
Detection was effected using a UV spectrometer at 210 nm.
Example 2
Heterogeneously catalysed hydrogenation: Hydrogenation of (lS,2S)-[2-chloro-
2-(3-methoxy-phenyI)-cycIohexyImethyl]-dimethylamine hydrochloride
3.18 kg (10 mol) (lS.2S)-[2-chloro-2-(3-methoxy-phenyl)-cyclohexylmethyl]
dimethylamine hydrochloride (from Example 1) were dissolved in 15 1 methanol.
and 350 g palladium on activated carbon 5% were added. Hydrogen was introduced
at normal pressure and ambient temperature until hydrogenation was complete. The
catalyst was suction filtered, the solvent concentrated to a small volume and the base
liberated using aqueous sodium hydroxide solution. After shaking out the aqueous
phase using ethyl acetate and distilling off the organic solvent 2.47 kg (100 % of
theoretical) (1 R.2R)-[2-(3-methoxyphenyl)-cyclohexylmethylamine]-dimethylamine
as a slightly yellow coloured oil remained.
The oil was dissolved in acetone and the hydrochloride precipitated using
hydrochloric acid gas. 2.27 kg (80 % of theoretical) (lR,2R)-[2-(3-methoxy-
phenyl)-cyclohexylmethylj-dimethylamine hydrochloride were obtained as a
colourless powder with a content of cyclohexylmethyl]-dimethylamine hydrochloride. which was removed from 2-
propanol by recrystallisation.
Identification was effected by comparing the analytical data of the product obtained
and the compound known from EP 0 753 506 Al, which exhibited identity. The
chemical and optical purity was analysed by HPLC on a Nucleosil 100-5 C8 HD
column (250 x 3 mm) by gradient elution with acetonitrile/water. Detection was
effected using a UV spectrometer at 210 nm.
Example 3
Methylether cleavage using methane sulphonic acid/methionine: Production of
(lR,2R)-3-(2-dimethyIaminomethyl-cyclohexyl)-phenol hydrochloride
2.83 kg (10 mol) (lR.2R)-[2-(3-methoxyphenyl)-cyclohexyl-methyl]-dimethylamine
hydrochloride were suspended in a mixture of 8.70 1 methane sulphonic acid and
1.50 kg (D.L) methionine and heated for 5 hours to 70° to 90°C. The mixture was
cooled to 30°C and adjusted using 32% aqueous sodium hydroxide solution to a pH
of 12 to 14. The base was extracted with ethyl acetate. After concentrating the
organic solvent and precipitation in acetone with hydrochloric acid gas (or aqueous
hydrochloric acid) 1.86 kg (80 %) (lR,2R)-3-(2-dimethylaminomethyl-cyclohexyl)-
phenol hydrochloride with a content of (methoxyphenyl)-cyclohexyl-methyl]-dimethylamine hydrochloride.
Recrystallisation from water produced colourless crystals (1.5 kg. 80 %) of (1R,2R)-
3-(2-dimethylaminomethyl-cyclohexyl)-phenol hydrochloride dihydrate.
Identification was effected by comparing the analytical data of the product obtained
and the compound known from EP 0 753 506 Al. which exhibited identity. The
chemical and optical purity was analysed by HPLC on a Nucleosil 100-5 C8 HD
column (250 x 3 mm) by gradient elution with acetonitrile/water. Detection was
effected using a UV spectrometer at 210 nm.
WE CLAIM:
1. Process for converting a tertiary OH group of an organic compound into
a tertiary Cl group of the organic compound, characterized in that the tertiary
alcohol is suspended or dissolved in a solvent selected from the group
comprising toluene, o-xylene, m-xylene, p-xylene and mixtures thereof,
thionyl chloride is added to the resultant suspension or solution, and the
resultant organic compound comprising the tertiary Cl group is then
separated from the further reaction components, the temperature range
and/or the reaction time required is 35-45°C and 1 to 4 hours.
2. Process as claimed in claim 1, wherein the organic compound
comprising the tertiary Cl group is obtained after the reaction has taken
place by distilling off the further reaction components with the solvent.
3. Process as claimed in claim 1, wherein the organic compound
comprising the tertiary Cl group is obtained as a solid after the reaction has
taken place by cooling to be tew ambient temperature, and is dried at
temperatures between 35°C and 75°C, preferably under vacuum.
4. Process for producing a compound of formula (I)

in the form of its racemates, its pure stereoisomers, in particular enanttomers or
diastereomers, or in the form of mixtures of stereoisomers, in particular the
enantiomers or diastereomers, in any mixing ratio; in the illustrated form or in
the form of its salts, in particular physiologically acceptable salts, particularly
preferably in the form of the hydrochloride, and/or in the form of its solvates, in
particular the hydrates;
wherein a compound of formula (II)

in the form of its racemates, its pure stereoisomers, in particular enantiomers or
diastereomers, or in the form of mixtures of stereoisomers, in particular the
enantiomers or diastereomers, in any mixing ratio; in the illustrated form or in
the form of its salts, in particular physiologically acceptable salts, particularly
preferably in the form of the hydrochloride, and/or in the form of its solvates, in
particular the hydrates;
(a) is suspended in a solvent, selected from the group comprising toluene,
o-xylene, m-xyiene, p-xylene and mixtures thereof;
(b) thionyl chloride is added to the resultant suspension; and
(c) the reaction product comprising the tertiary Cl group of formula (I) is
separated from the further reaction components.
5. Process as claimed in claim 4, wherein the reaction product of formula (I)
is separated (c) by distilling off the solvent with the further reaction
components.
6. Process as claimed in claim 4, wherein separation (c) is effected by
precipitating the reaction product of formula (I) by cooling the reaction
mixture to below ambient temperature and then drying the reaction product
at temperatures between 35°C and 75°C, preferably under vacuum.
7. Process as claimed in any one of claims 1 to 6 wherein solvent is toluene.
8. Process as claimed in any one of claims 1 to 7, wherein 1 to 2
equivalents, in particular 1.5 to 1.7 equivalents, particularly preferably 1.6
equivalents of thionyl chloride - based on the compound of formula (XI)- are
used.
9. Process as claimed in any one of claims 1 to 8, wherein reaction is carried
out with thionyl chloride at a temperature of 30 to 50°C, preferably 35 to
45% for 1 to 4 hours, preferably 2 to 3 hours.
10. Process as claimed in any one of claims 3 to 9, wherein the compound
(II) has the configuration (IIa) and/or (IIb):
11. Process as claimed in any one of claims 3 to 10, wherein the
compound (n) is used as an enantiomer with the absolute configuration
(IIa):
12. Process as claimed in any one of claims 3 to 11, for producing a
compound of general formula (HI)

in the form of its racemates, its pure stereoisomers, in particular enantiomers
or diastereomers, or in the form of mixtures of stereoisomers, in particular the
enantiomers or diastereomers, in any mixing ratio; in the illustrated form or in
the form of its salts, in particular physiologically acceptable salts, particularly
preferably in the form of the hydrochloride, and/or in the form of its solvates, in
particular the hydrates: wherein the compound of formula (I) in a step
(d) is subjected to catalytic hydrogenation with palladium on activated carbon
as the catalyst.
13. Process as claimed in claim 12, wherein hydrogenation (d) is carried out
while retaining stereochemistry on the carbon atom marked by an asterisk (*) in
formula (I) or (IE).
14. Process as claimed in either of claims 12 or 13, for producing a
compound (IV)
in the form of its racemates, its pure stereoisomers, in particular enantiomers or
diastereomers, or in the form of mixtures of stereoisomers, in particular the
enantiomers or diastereomers, in any mixing ratio; in the illustrated form or in
the form of its salts, in particular the physiologically acceptable salts, particularly
preferably in the form of the hydrochloride, or in the form of its solvates, in
particular the hydrates; characterized in that the compound (EC), in the form of
its race mates, its pure stereoisomers, in particular enantiomers or diastereomers,
or in the form of mixture of stereoisomers, in particular the enantiomers or
diastereomers, in any mixing ratio; in the illustrated form or in the form of its
salts, in particular physiologically acceptable salts, particularly preferably in the
form of the hydrochloride, and/or in the form of its soivates, in particular the
hydrates; in a step
(e) is subjected to methyl ether cleavage with methionine/methane sulphonic
acid.
15. Process as claimed in claim 14, wherein starting from the compound
with the absolute configuration (Ha),

by carrying out the process steps (a) to (e) the compound with the absolute
configuration (IVa)
is produced in the form of its hydrochloride and/or its hydrochloride hydrate.
Process for converting a tertiary OH group of an organic compound into a
tertiary Cl group of the organic compound, characterized in that the tertiary
alcohol is suspended or dissolved in a solvent selected from the group
comprising toluene, o-xylene, m-xylene, p-xylene and mixtures thereof,
thionyl chloride is added to the resultant suspension or solution, and the
resultant organic compound comprising the tertiary Cl group is then
separated from the further reaction components, the temperature range
and/or the reaction time required is 35-45°C and 1 to 4 hours.

Documents:

1760-KOLNP-2004-FORM-27.pdf

1760-kolnp-2004-granted-abstract.pdf

1760-kolnp-2004-granted-claims.pdf

1760-kolnp-2004-granted-correspondence.pdf

1760-kolnp-2004-granted-description (complete).pdf

1760-kolnp-2004-granted-examination report.pdf

1760-kolnp-2004-granted-form 1.pdf

1760-kolnp-2004-granted-form 18.pdf

1760-kolnp-2004-granted-form 2.pdf

1760-kolnp-2004-granted-form 26.pdf

1760-kolnp-2004-granted-form 3.pdf

1760-kolnp-2004-granted-form 5.pdf

1760-kolnp-2004-granted-reply to examination report.pdf

1760-kolnp-2004-granted-specification.pdf

1760-kolnp-2004-granted-translated copy of priority document.pdf


Patent Number 222893
Indian Patent Application Number 1760/KOLNP/2004
PG Journal Number 35/2008
Publication Date 29-Aug-2008
Grant Date 27-Aug-2008
Date of Filing 19-Nov-2004
Name of Patentee GRUNENTHAL GMBH
Applicant Address ZIEGLERSTRASSE 6 52078 AACHEN
Inventors:
# Inventor's Name Inventor's Address
1 BUSCHMANN, HELMUT CARRER EST, 24,08950 ESPLUGUES DE LLOBREGAT
2 HELL, WOLFGANG MARSHALLSTRASSE 10, 52066 AACHEN
3 KEGEL, MARKUS ERBERICHSHOTSTRASSE 67, 52078 AACHEN
PCT International Classification Number C07C 217/54, 213/08
PCT International Application Number PCT/EP03/04213
PCT International Filing date 2003-04-23
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 10218862.9 2002-04-26 Germany