AN IMPROVED PROCESS FOR THE PREPAMTION OF OXCARBAZEPINE
Field of Invention
The present invention relates to an improved process for the preparation of pure I O-oxo-
10,l I -dihydro-5H~dibenz[b,r]azepi1~e-S~~arboxam(iodxec arbazepine). Specifically, the
present invention relates to an improved process for the preparation of 10-methoxy-5Hdibenz[
bfazepine, which is further converted to oxcarbazepine. In general the present
invention provides a process for the preparation of pure oxcarbazepine, substantially free
of impurities without involving the cumbersome purification steps.
Background of the Invention
10-0x0- 10,ll -dihydro-5H-dibenz[b,flazepine-5-carboxamide (oxcarbazepine),
compound of formula [I], possesses valuable properties for the treatment of epilepsy
(US371 6640) and has been proposed for use in the treatment of psychosomatic diseases
and trigeminal neuralgia. It has also been proposed for use in the treatment of
parkinsonian syndromes as described in US 5,658,900, and AIDS-related neural disorders
as described in WO 94/20] 10.
1
Several processes for preparing oxcarbazepine have been reported in the prior art
literature.
US 3,642,775 describes the preparation of oxcarbazepine from 10-methoxy iminostilbene
f
[11] by reaction with phosgene in toluene, followed by amidation (ethanol and ammonia)
and hydrolysis in acidic medium to get desired product (Scheme 1).
Reaction of phosgene with 10-methoxy iminostilbene [II] is carried out at relatively high
temperatures of around 9.5"~ and the hydrochloric acid produced leads to the formation
of undesirable impurities. The process uses phosgene gas, which is toxic and hazardous,
requiring extreme precaution, making this process commercially unviable.
Scheme 1
CA 1 ,I 12,241 describes an alternate preparation of oxcarbazepine from the catalyzed rearrangement
of 10,Il-epoxycarbamazepine [VI], which itself is prepared from
carbamazepine by reaction with m-chloroperbenzoic acid (m-CPBA) (Scheme 2). The
disadvantage of this process is the use of carbamazepine as starting material, which is an
expensive raw material. Another disadvantage is that the yield and quality of the epoxide
is very low, making the process unviable.
Scheme 2
CUNH2 COW,
EP 028028, discloses a process involving nitration of 5- cyanoiminostilbene [VIII]
followed by reduction and hydrolysis (Scheme 3). However, the drawback of the process
is in the' preparation of the 5-cyanoiminostilbene itself, which can be made from
iminostilbene [VII] and cyanogen chloride. The latter is also toxic, hazardous and
difficult to handle on commercial scale.
Scheme 3
CIcN Nitration a N ' I I
[ v I ~ ] 11x1
Reduction
US 20050282797 describes the synthesis of oxcarbazepine by reacting oxi'minostilbene
[XI] with chlorosulfonyl isocyanate in an inert organic solvent to give the intermediate of
formula [XII], which on hydrolysis gives oxcarbazepine [I] (Scheme 4).
Scheme 4
-
The major drawback of this process is that preparation of oximinostilbene [XI], which
requires harsh conditions and involves a tedious work-up procedure. Moreover,
chlorosulfonyl isocyanate is an expensive, highly moisture sensitive and toxic reagent
and also the reaction with chlorosulfonyl isocyanate and subsequent hydrolysis requires a
relatively complicated isolation procedure and th~isg ives low yield.
US 5,808,058 describes a process, which involves the carbamoylation of 10-
methoxyiminostilbene [11] to give 1 O-methoxycarbamazepine [IV]. This is achieved using
an alkali metal cyanate like sodium cyanate and a relatively strong organic or inorganic
acid, preferably acetic acid. The carbamoylation followed by hydrolysis of the enol-ether
group under mildly acidic aqueous conditions to furnish oxcarbazepine gives poor yield.
(Scheme 5).
Scheme 5
Desired
Undesired
US 6,670,472 describes the synthesis of oxcarbazepine [I], by reacting 10-
methoxyiminostilbene of formula [II] with an alkali metal cyanate and a mild acidic
reagent, followed by the hydrolysis with a dilute mineral acid.
The drawback of both the above mentioned processes is that under the above
carbamoylatioh conditions, a concomitant reaction,. hydrolysis of the enol-ether group of
10-methoxyiminostilbene [II] to the corresponding ketone of formula [XI] prior to
carbamoylation, also occurs. Once formed, the compound of formula [XI] does not
undergo further conversion to oxcarbazepine in the presence of the metal cyanate and
acid. Consequently, a mixture of products and related impurities a.re prod~~cedw,h ich
requires a tedious and uneconomical purification procedure, which results in low yields
(28% to 65%) of final oxcarbazepine. Also, to obtain the purity of desired level the
multiple purification steps such as multiple crystallization is required, which results in
loss of yield.
It is known that synthetic compounds can contain extraneous compounds or impurities
resulting during the synthetic steps or degradation products. The impurities can be
unreacted starting materials, by-products of the reaction, products of side reactions, or
degradation products. Generally, impurities in an active pharmaceutical ingredient (API)
may arise from degradation of the API itself, or during the preparation of the API.
Impurities in oxcarbazepine or any active pharmaceutical ingredient (API) are
undesirable and might be harmful.
The product mixture of a chemical reaction is rarely a single compound with sufficient
purity to comply with pharmaceutical standards. Side products and byproducts of the
reaction and adjunct reagents used in the reaction can, in most cases, also be present in
the product mixture. At certain stages during processing of the active pharmaceutical
ingredient, the product must be analyzed for purity, typically, by HPLC, TLC or GC
analysis, to determine if it is suitable for continued processing and, ultimately, for use in
a pharmaceutical product. Purity standards are set with the intention of ensuring that an
API is as free of impurities as possible, and, thus, is as safe as possible for clinical use.
Oxcarbazepine obtained by the processes described in the arts (Scheme 4 and 5) are not
satisfactory from a purity perspective. Reproduction of the oxcarbazepine according to
synthetic procedures as described in these prior arts show that unacceptable amounts of
6
--
impurities are generally formed along with ox~arbazepine,w hereas for the removal of
these impurities requires purification steps such as multiple crystallizations are required,
which decrease the yield.
Therefore, there is a need for an industrially feasible and cost effective process for the
preparation of pure oxcarbazepine, which involves minimum chemical steps, shorter time
cycle and which does not involve the cumbersome purification steps to obtain desired
purity level, at the same time with minimal loss of yield. The present invention provides
an industrially feasible process for the preparation of oxcarbazepine, which involves
minimum time consumption, is economical by use of inexpensive reagents and gives
overall good yield and purity.
Brief Description of the Invention
In one aspect, provided herein is a pure oxcarbazepine substantially free of impurities
without involving multiple crystallizations or isolation steps.
In still further aspect, encompassed herein is a process for preparing the pure
oxcarbazepine substantially free of impurities.
In still another aspect, provided herein, is a process for the preparation of 10-methoxy-
5H-dibenz[bfazepine, which is further converted to oxcarbazepine.
In still another aspect, provided herein, is a process for the preparation of 10-methoxy-
5H-dibenz[b,Jlazepine, which comprises in-situ preparation starting from iminostilbene
carbonyl chloride.
In still another aspect, provided herein, is a process for the preparation of IO-methoxy-
5H-dibenz[bdazepine, which comprises in-situ preparation starting from mixture of
iminostilbene carbonyl chloride and iminostilbene carbonyl bromide.
In still another aspect, provided herein, is a pharmaceutical composition comprising pure
oxcarbazepine substantially free of impurities made by the process disclosed herein, and
one or more pharmaceutically acceptable excipients.
In yet another aspect there is provided a use of a pharmaceutical composition that
includes a therapeutically effective amount, of oxcarbazepine prepared according to the
process of the present invention and one or more pharmaceutically acceptable carriers,
excipients or diluents to treat conditions in a subject, in need thereof such as treatment of
psychosomatic diseases, trigeminal neuralgia or in the. treatment of parkinsonian
syndromes and the like.
Detailed Description of the Invention
As used herein "pure oxcarbazepine substantially free of 'impurities" refers to
oxcarbazepine having a purity of about 99.5% to about 99.99% and further comprising
impurities in an amount of less than about 0.5%. Specifically, the oxcarbazepine, as ,
disclosed herein, contains less than about 0.1 % of impurities. The content of impurities
can be measured by the analytical techniques such as high performance liquid
chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS).
In one aspect, provided herein is a pure oxcarbazepine substantially free of impurities
without involving multiple isolation steps.
According to another aspect, there is provided a process for the preparation of 10-alkoxy-
5H-dibenz[b,Jlazepine, comprising the steps of:
(a) providing a solution of iminostilbene carbonyl chloride or iminostilbene carbonyl
bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
- -
(c) optionally, treating the solution of step (b) with solution of alkali or alkaline earth
metal thiosulphate or bicarbonate or both;
(d) treating the reaction mixture with a base in presence of an alcoholic solvent to
obtain 1 O-alkoxy-5H-dibenz[b,flazepine.
According to another aspect, there is provided a process for the preparation of 10-
methoxy-5H-dibenz[b, flazepine, comprising the steps of:
(a) providing a solution of iminostilbene carbonyl chloride or iminostilbene carbonyl
bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
(c) optionally, treating the solution of step (b) with solution of alkali or alkaline earth
metal thiosulphate or bicarbonate or both and
(d) treating the reaction mixture with a base in presence of methanol to obtain 10-
methoxy-5H-dibenz[b,Aazepine.
According to another aspect, there is provided a process for the preparation of
oxcarbazepine, comprising the steps of:
(a) providing a solution of iminostilbene carbonyl chloride or iminostilbene carbonyl
bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
(c) optionally, treating the solution of step (b) with solution of alkali or alkaline earth
metal thiosulphate or bicarbonate or both;
(d) treating the reaction mixture with a base in presence of an alcoholic solvent to
obtain I O-alkoxy-5H-dibenz[b,Jlazepine and
(e) converting of 1 O-alkoxy-5H-dibenz[b, Aazepine to oxcarbazepine.
According to another aspect, there is provided a process for the preparation of
oxcarbazepine, comprising the steps of
(a) providing a solution of iminostilbene carbonyl chloride or iminostilbene
carbonyl bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
(c) optionally, treating the solution of step (b) with solution of alkali or alkaline
earth metal thiosulphate or bicarbonate or both;
(d) treating the reaction mixture obtained in step (b) or (c) with a base in presence
of alcoholic solvent to obtain 1 O-alkoxy-5H-dibenz[bfazepine;
(e) carrying out carboxamidation of 10-alkoxy-5H-dibenz[b,jJazepine with an
alkali metal cyanate and an acid in presence of a suitable solvent to obtain 10-
I
(f) hydrolyzing 10-alkoxy-5H-dibenz[b,jJazepine-5-carboxamidoeb tained in step
(el;
(g) obtaining oxprbazepine from the solution and
(h) optionally, recrystallizing the oxcarbazepine.
According to another aspect, there is provided a process for the preparation of
oxcarbazepine, comprising the steps of:
(a) providing a solution of iminostilbene carbonyl chloride or iminostilbene
carbonyl bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
(c) treating the reaction mixture of step (b) with solution of sodium thiosulphate;
(d) treating the reaction mixture of step (c) with solution of sodium bicarbonate;
(e) treating the reaction mixture obtained in step (d) with a base in presence of
methanol to obtain 1 O-methoxy-5H-dibenz[b,Jlazepine;
(f) carrying out carboxamidation of I O-methoxy-5H-dibenz[b,Jlazepine with an
alkali metal cyanate and an acid in presence of a suitable solvent to obtain 10-
methoxy-5H-dibenz[b,Jlazepine-Scarboxamide;
(g) hydrolyzing 1 O-methoxy-5H-dibenz[bfazepine-5-carboxamide obtained in
step (0;
(h) obtaining oxcarbazepine from the solution and
(i) optionally, recrystallizing the oxcarbazepine.
Scheme 6
(XIII) (XIV)
R= COCl or COBr or
Mixture
OCH3
purification
P
I I
CONH2 I
CONH2 I
CONH2
(1) (1) (1V)
The suitable solvent as defined above can be selected from the group comprising of
nitriles, ketones, esters, halogenated hydrocarbons, ethers, amides, dialkylsulfoxides,
hydrocarbons, or the mixtures thereof. Nitriles are selected from the group comprising of
acetonitrile, propionitrile, butyronitrile, valeronitrile and the like, preferably acetonitrile.
Ketones are selected from the group comprising of acetone, methyl ethyl ketone, methyl
isobutyl ketone and the like.
Bromination can be carried out in presence of a brominating agent capable of
brominating an alkene viz. liquid bromine, pyridinium tribromide etc.
A suitable base as defined above can be inorganic base selected from group comprising
of carbonates, bicarbonates, of alkali and alkaline earth metal and the like. Carbonates are
selected from the group comprising of K2CO3, Cs2C03 and Na2C03 etc. Bicarbonates are
selected from the group comprising of NaHC03, KHCO3 etc.
The alcohol solvent as defined above include, but are not limited to, CI to Cg straight or
branched chain alcohol solvents such as methanol, ethanol, n-propanol, isopropanol, n-
12
butanol, isobutanol, tert-butanol, amyl alcohol, isoamyl alcohol, hexanol, or mixtures
thereof. A specific alcohol solvent is methanol, ethanol, n-propanol or isopropanol:
Carboxamidation of 1 0-alkoxyiminostilbene according to the present invention comprises
reacting 10-alkoxyiminostibene with HOCN in presence of organic medium, wherein the
disclosed cyanates include sodium or potassium cyanate, preferably sodium cyanate and
said organic medium is selected from an aromatic hydrocarbon solvent or an aliphatic
chlorinated solvent such as benzene, toluene, xylene or dichloromethane. The generation
of cyanate is performed in situ by the reaction of alkali metal cyanate with a mild acidic
reagent. The acidic reagent is preferably a weak acid, such as an aromatic acid. Preferred
aromatic acids include weak non-aliphatic organic acids such as benzoic acid or halo
substituted benzoic acids; suitable'substituents being halo especially chloro e.g. parachlorobenzoic
acid. Excess molar quantity of the weak acid is preferably used in
comparison to 10-alkoxyiminostilbene, in the range of from 2 to 10 molar excess,
preferably about 5 to 8 times. Further the reaction is carried out employing an organic
medium, preferably under reflux conditions. The organic medium is selected from
aromatic hydrocarbon solvent or aliphatic chlorinated solvent, preferably benzene,
toluene, xylene or dichloromethane.
The hydrolysis is carried out in presence of a suitable acid or base in accordance with one
preferred embodiment of the present invention, wherein the preferred acid is selected
from mineral acids, lower alkane or halogenated lower alkanecarboxylic acids having up
to 4 carbon atoms, more preferably hydrochloric acid, sulfuric acid, polyphosphoric acid,
acetic acid or trichloro or trifluoroacetic acid alone or in combination thereof. The
preferred base employed in this reaction is selected from alkoxides, hydroxides,
carbonates or bicarbonate of alkali or alkaline earth metal alone or in combination
thereof, wherein, the said alkali or alkaline earth metal is preferably selected from Li, Na,
K, Ca or Mg.
I
According to the present invention, the mixture of iminostilbene carbonyl chloride and
iminostilbene carbonyl bromide is in any possible combination, preferably in the ratio of
7:3.
I
The recrystallization of oxcarbazepine is carried out by using a solvent selected from the
group comprising of alcohols, nitriles, ketones, esters, ethers, amides, dialk.ylsulfoxide,
water or the mixtures thereof. Alcohols are selected from the group comprising of
methanol, ethanol, n-propanol, isopropanol, n-butanol and the like. The nitriles are
selected from the group comprising .of acetonitrile, propionitrile, butyronitrile,
valeronitrile and the like. Ketones are selected from the group comprising of acetone,
methyl ethyl ketone, methyl isobutyl ketone etc. Esters are selected from the group
comprising of ethyl acetate, propyl acetate and the like. Chlorinated solvents are selected
from the group comprising of dichloromethane, chloroform, dichloroethane,
chlorobenzene and the like. Ethers can be selected fiom the group comprising of diethyl
ether, diisopropyl ether, tetrahydrofuran, dioxane and the like. Amides can be selected
from the group comprising of dimethylformamide, dimethylacetamide, N-methyl
formamide, N-methyl pyrrolidine and the like. Dialkyl sulfoxide can be selected from the
group comprising of dimethyl sulfoxide, sulfolane diethyl sulfoxide, dibutyl sulfoxide
and thk like.
In another aspect there is provided a pharmaceutical composition that includes a
therapeutically effective amount of oxcarbazepine according to the process of the present
invention and one or more pharmaceutically acceptable carriers, excipients or diluents.
In yet another aspect there is provided a use of a pharmaceutical composition that
' includes a therapeutically effective amount of oxcarbazepine according to the process of
the present invention and one or more pharmaceutically acceptable carriers, excipients or
diluents to treat conditions in a subject, in need thereof such as treatment of
- psychosomatic diseases, trigeminal neuralgia or in. the treatment of parkinsonian
syndromes and the like.
14
- ,
The details of the process of the invention are provided in the Examples given below,
which are provided by way of illustration only and therefore should not be constructed to
limit the scope of the invention.
Examples:
Example 1
Preparation of 10-methoxy-5H-dibenz[bJlazepine
A solution of iminostilbene carbonyl chloride (mixture of chloride + bromide ratio is
-7:3) (50.0g) in methylene dichloride (300mL) was stirred for about 15-20 minutes
at about 2530°C. Cooled the reaction mass to 5-10°C. Charged-'the solution of
bromine (35.6~)in methylene dichlnride (50mTa)n ver a perind of 30-45 min by
maintaining the temperature between 5-10°C. Maintained the.reaction mass at 5-
10°C for 2h. Allowed the reaction mass to attain 25-30°C and maintained for 2h.
Slowly charged sodium thiosulphate solution (100mL) over a period of 15-20min
at 25-30°C. Reaction mass was stirred at 25-30°C for 30min and separated the
layers. Washed the MDC layer with 50mL of DM water at 25-30°C. Charged
sodium bicarbonate solution (50mL) to methylene dichloride layer followed by
stirring. Separated the layers and charged water (50mL) to methylene dichloride
layer, stirred at 2530°C for 30min and separated the layers. Distilled methylene
dichloride and charged toluene (50mL) to the residue and distilled out toluene
under vacuum at 60-65°C. Degassed the residual mass for 30min. To the residue,
charged toluene (500mL) at 25-30°C followed with addition of KOH flakes (73g)
and NaOH flakes (44.7g) at 25-30°C. Slowly charged methanol (150mL) and
heated the reaction mass to reflux and maintained for 24-30h. Cooled the reaction
mass to 25-30°C followed by addition of water (400mL). Separated the layers and
washed the toluene layer with 2X150mL and 1x50 mL O ~ D M water. The toluene
layer was distilled under vacuum at 60-65°C. Charged IPA (25mL) and distilled
IPA under vacuum at 60-65°C and degassed for 30min. Charged IPA (200mL) to
the residue at 2530°C and heated to reflux for 30min. Allowed the reaction mass
to attain 2530°C and maintained at about 2530°C for about 8h. Cooled to about
0-5°C and maintained at 0-5°C for about 2h. Filtered the reaction mass, washed
with cold IPA (25mL) and suck dried to obtain the title compound. Yield 34 g;
purity 99.59%.
- 16 ,
Example 2
Preparation of crude 10-0x0-10, 11-dihydro-SH-dibenz [bflazepine -5-caboxamide
from 10-methoxy-SH-dibenz[bJl azepine:
10-methoxy-5H-dibenz[b,Jlazepine (70g, 0.3 135mol) in toluene and sodium cyanate
(7 1.40g, 1.098mol), benzoic acid (1 34.0g, 1.090 1 mol) were charged and stirred at 85-
90°C for I Ohrs. Quenched the reaction mass with 10% sodium hydroxide solution, stirred
at RT, further cooled to 0-5°C and filtered, washed with toluene followed by water till
neutral pH, dried at 80°C under vacuum to get 10-methoxy-5H-dibenz[b,Jlazepine-5-
carboxamide. Above material was taken in methanol (4V) and DM water (IV), refluxed
and distilled out 2V methanol from the reaction mass, charged DM water (3V) and con.
HCI (0.19V) at RT. Stirred the reaction mass at 7580°C for 6hr, cooled and filtered at
RT, washed with sodium bicarbonate solution (5%) followed by DM water and methanol.
Dried the material at 50-60°C to afford crude 10-0x0-1 0,ll -dihydro-5Hdibenz[
b,flazepine-5-caboxamide.Y ield: 60.0g. Purity: 99.64%.
Example 3
Purification of crude 10-0x0-10,ll-dihydro-5H-dibenz[b flazepine -5-caboxamide:
Crude 10-0x0- 10,11 -dihydro-5H-dibenz[b,flazepine-5-caboxamide (60.0g, 0.2378mol)
was purified in methanol by adjusting pH 8-9 using triethylamine and refluxed for 4hr.
Filtered at RT to get semi pure 10-0x0-10,ll-dihydro-5H-dibenz[b,Jlazepine-5-
caboxamide which was further purified in DCM and methanol mixture (I:]) to get pure
10-oxo-lO, l 1-dihydro-5H-dibenz[b,flazepine-5-caboxamide. Yield: 5 1.50g. Purity:
99.97%.
Claims:
1. A process for the preparation of oxcarbazepine, comprising the steps of:
(a) providing a solution of iminostilbene carbonyl chloride or iminostilbene
carbonyl bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
(c) optionally, treating the solution of step (b) with solution of alkali or alkaline
.
earth metal thiosulphate or bicarbonate or both;
(d) treating the reaction mixture with a base in presence of an alcoholic solvent to
obtain 1 0-alkoxyf5H-dibenz[b,Jlazepine and
-'.
(e) converting of 10-alkoxy-5H-dibenz[bfazepine to oxcarbazepine.
2. The process according to claim 1, wherein bromination is carried out using liquid
bromine or pyridinium tribromide.
3. The process according to claim 1, wherein alkali or alkaline earth metal
thiosulphate or bicarbonate are sodium or potassium thiosulphate or sodium or
potassium bicarbonate.
4. The process according to claim 1, wherein alcoholic solvent in step (d) is selected
,from -the group comprising of methanol, ethanol, n-propanol, isopropanol, nbutanol,
isobutanol, tert-butanol, amyl alcohol, isoamyl alcohol, hexanol, and
mixtures thereof.
5. The process according to claim 4, wherein solvent is methanol.
6. A process for the preparation of oxcarbazepine, comprising the steps of:
(a) providing a solution of iminostilbene carbonyl chloride or iminostilbene
carbonyl bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
(c) optionally, treating the solution' of step (b) with solution of alkali or alkaline
earth metal thiosulphate or bicarbonate or both;
(d) treating the reaction mixture obtained in step (b) or (c) with a base in
presence of alcoholic solvent to obtain 10-alkoxy-5H-dibenz[b,Jlazepine;
(e) carrying out carboxamidation of 10-alkoxy-5H-dibenz[b,Jlazepine with an
alkali metal cyanate and an acid in presence of a suitable solvent to obtain 10-
alkoxy-5H-dibenz[b,Jlazepine-5-carboxamide;
(f) hydrolyzing 10-alkoxy-5H-dibenz[b,flazepine-5-carboxamide obtained in
step (4;
(g) obtaining oxcarbazepine from the solution and
(h) optionally, recrystallizing the oxcarbazepine.
7. A process for the preparation of oxcarbazepine, comprising the steps of:
(a) providing ,a solution of iminostilbene carbonyl chloride or iminostilbene
carbonyl bromide or mixture thereof in a suitable solvent;
(b) brominating the reaction mixture obtained in step (a);
(c) treating the reaction mixture of step (b) with solution of sodium thiosulphate;
(d) treating the reaction mixture of step (c) with solution of sodium bicarbonate;
(e) treating the reaction mixture obtained in step (d) with a base in presence of
methanol to obtain 10-met.hoxy-SH-dihcnz[h,Jla7.epine,
(0 carrying out carboxamidation of 10-methoxy-5H-dibenz[bfazepine with an
alkali metal cyanate and an acid in presence of a suitable solvent to obtain 10-
methoxy-5H-dibenz[b,Jlazepine-5-carboxamide;
(g) hydrolyzing 10-methoxy-5H-dibenz[b,Jlazepine-5-carboxamideo btained in
step (f);
(h) obtaining oxcarbazepine from the solution and
(i) optionally, recrystallizing the oxcarbazepine.
8. The process according to claim 7, wherein recrystallization of oxcarbazepine
is carried out by using a solvent selected from the group comprising of
alcohols, nitriles, ketones, esters, ethers, amides, dialkylsulfoxide, water or the
mixtures thereof.
9. The pharmaceutical composition that includes a therapeutically effective
amount of oxcarbazepine, prepared according to process of claim 1, and one
or more pharmaceutically acceptable carriers, excipients or diluents.
10. Use of a pharmaceutical composition that. incl~ldesa therapeutically effective
amount of oxcarbazepine,. prepared according to process of claim 1,
f
acceptable carriers, excipients or diluents to treat conditions in a subject, in
need thereof such as treatment of psychosomatic diseases, trigeminal
neuralgia or in the treatment of parkinsonian syndromes and the like.