DESC:FIELD OF INVENTION
The present invention relates to process for the preparation of pure 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (oxcarbazepine). Specifically, the present invention relates to process for the preparation of 10-methoxy-5H-dibenz[b,f]azepine from iminodibenzyl, which is further converted to oxcarbazepine, substantially free of impurities.
BACKGROUND OF THE INVENTION
10-Oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (oxcarbazepine), compound of formula [I], is an anticonvulsant and is currently marketed by Novartis Pharmaceuticals under the branded name TRILEPTAL®.

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 [II] by reaction with phosgene in toluene, followed by amidation (ethanol and ammonia) and hydrolysis in acidic medium to get desired product (Scheme 1). The process uses phosgene gas, which is toxic and hazardous, requiring extreme precaution, making this process commercially unviable.
Scheme 1

CA 1,112,241 describes an alternate preparation of oxcarbazepine from the catalyzed re-arrangement of 10,11-epoxycarbamazepine [VI], which itself is prepared from carbamazepine [V] 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 compound [VI] is very low, making the process unviable.
Scheme 2

EP0028028, discloses a process, which involves 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 [VIII] itself, which can be made from iminostilbene [VII] and cyanogen chloride. Cyanogen chloride is also toxic, hazardous and difficult to handle on commercial scale.
Scheme 3

US 20050282797 describes the synthesis of oxcarbazepine by reacting oximinostilbene [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. Further, the reaction with chlorosulfonyl isocyanate and subsequent hydrolysis requires a relatively complicated isolation procedure and thus gives low yield.

US 5,808,058 describes a process, which involves the carbamoylation of 10-methoxyiminostilbene [II] to give 10-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 in poor yield. (Scheme 5).
Scheme 5

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.

CN102432539A, CN101307021, CN102120729A and US 3,531,466 discloses processes of producing iminostilbene through catalytic dehydrogenation of iminodibenzyl at very high temperature, using different types of dehydrogenation catalyst in different type of reactors.

GB943277 discloses a process for the preparation of compound of formula II from compound of formula XIII. The process discloses reacting compound of formula XIII with alkali metal hydroxide to yield monobromoazepine compound of formula XIV after 14 hours at room temperature, which is then refluxed with excess alkali metal alkanoate for 18 hours to result in compound of formula II. This patent also discloses direct conversion of compound of formula XIII to compound of formula II in about 32-40 hours. (Scheme 6).

Scheme 6

Swiss Pat. No. 642,950 describes the synthesis of oxcarbazepine starting from a compound of formula VII followed by halogenation, treatment with alkali metal alkoxide and acid hydrolysis (Scheme 7).
Scheme 7

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 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 impurities are generally formed along with oxcarbazepine. For the removal of these impurities, 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.

Therefore, present invention provides a synthetic method for the preparation of 10-methoxy iminostilbene and further to oxcarbazepine, to overcome the deficiencies of prior art processes. The method comprising selecting reaction conditions during bromination of iminodibenzyl carbonyl chloride, which improve the utilization ratio of brominating agent and further reduces the safety requirements in production process. Further, process of present invention reduces bromide/chloride quantity discharge, which is beneficial to environmental protection.

OBJECT OF THE INVENTION

It is a principal object of the present invention to improve upon limitations of the prior arts by providing an efficient process for the preparation of 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[b,f]azepine, which is further converted to oxcarbazepine.

In still another aspect, provided herein, is a process for the preparation of iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide starting from iminodibenzyl compound.

In still another aspect, provided herein, is a process for the preparation of iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide, which comprises in-situ preparation starting from iminodibenzyl compound.

In still another aspect, provided herein, is a process for the preparation of 10-methoxy-5H-dibenz[b,f]azepine, which comprises in-situ preparation starting from iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide.

In still another aspect, provided herein, is a process for the preparation of iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide, which comprises reaction of iminodibenzyl carbonyl chloride with liquid bromine in presence of sodium bromate and radical initiator.

In still another aspect, provided herein, is a process for the preparation of iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide, which comprises reaction of iminodibenzyl carbonyl chloride with liquid bromine in presence of sodium bromate and radical initiator at 65-75°C to obtain intermediate compound, which is further heated at 90-100°C.

In still another aspect, provided herein, is a process for the preparation of 10-methoxy-5H-dibenz[b,f]azepine starting from mixture of iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide.

In still another aspect, provided herein, is a process for the preparation of 10-methoxy-5H-dibenz[b,f]azepine, which comprises in-situ preparation starting from mixture of iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide.

In yet another aspect, provided herein, is a process for the preparation of oxcarbazepine of formula [I] via iminodibenzyl carbonyl chloride, wherein iminodibenzyl carbonyl chloride is prepared by reacting iminodibenzyl with triphosgene.

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.

SUMMARY OF THE INVENTION
The present invention relates to a process for the preparation of oxcarbazepine substantially free of impurities.

In accordance with one preferred embodiment of the present invention, there is provided an economically viable and cost effective process for preparation of oxcarbazepine of formula [I], the process comprising preparing iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide, which is further converted to oxcarbazepine of formula [I].

In accordance with another embodiment of the present invention, there is provided a process for producing oxcarbazepine of formula [I] via an intermediate i.e. iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide, wherein said intermediate is prepared by reacting iminodibenzyl carbonyl chloride with liquid bromine employing use of sodium bromate and radical initiator.

In accordance with yet another embodiment of the present invention, there is provided a process for the preparation of iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide, which comprises reaction of iminodibenzyl carbonyl chloride with liquid bromine in presence of sodium bromate and radical initiator.

In accordance with another embodiment of the present invention, there is provided a process for producing oxcarbazepine of formula [I] via an intermediate i.e. iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide, wherein said intermediate is prepared by reacting iminodibenzyl carbonyl chloride with liquid bromine employing use of sodium bromate and radical initiator at a temperature of about 65-75°C to obtain an intermediate compound, which is further heated at 90-100°C.

In accordance with yet another embodiment of the present invention, there is provided a process for producing oxcarbazepine of formula [I] via iminodibenzyl carbonyl chloride, wherein iminodibenzyl carbonyl chloride is prepared by reacting iminodibenzyl compound with triphosgene.

In accordance with yet another embodiment of the present invention, there is provided a process for producing oxcarbazepine of formula [I] via 10-methoxy iminostilbene, wherein 10-methoxy iminostilbene is prepared by reacting iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide with liquid bromine at about -5 to 30°C to provide 10,11-Dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride, which is further reacted with methanol in presence of sodium hydroxide or potassium hydroxide.

In accordance with yet another embodiment of the present invention, there is provided a process for producing oxcarbazepine of formula [I] via 10-methoxy iminostilbene, wherein 10-methoxy iminostilbene is prepared by reacting iminodibenzyl with triphosgene followed by reaction with liquid bromine employing use of sodium bromate and a radical initiator at a temperature of about 65-75°C to obtain an intermediate compound, which is further heated at 90-100°C to obtain iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide. Thus obtained iminostilbene carbonyl chloride and/or its mixture with iminostilbene carbonyl bromide is further reacted with liquid bromine at about -5°C to 30°C to provide 10,11-Dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride which is further reacted with methanol in presence of sodium hydroxide or potassium hydroxide to obtain 10-methoxy iminostilbene.

DETAILED DESCRIPTION OF THE INVENTION
While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.

The disclosed embodiment of the present invention deals with a process for the preparation of 10-methoxy iminostilbene useful in preparing anti-convulsant oxcarbazepine [1], which is economically viable and cost effective and thus obviates the disadvantages mentioned in prior art.

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 is measured by the analytical techniques such as high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS).

Scheme 8

According to present invention, there is provided a process for the preparation of oxcarbazepine, comprising the steps of:
(i) reacting iminodibenzyl compound of formula [XXI] with triphosgene in presence of solvent to obtain 10,11-Dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride compound of formula [XXII];

(ii) reacting iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate, radical initiator and solvent to obtain 5H-dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide; and

(iii) converting of 5H-Dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide to oxcarbazepine [I].

According to another aspect, there is provided a process for the preparation of oxcarbazepine, comprising the steps of:
(i) reacting iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate, radical initiator and solvent to obtain 5H-dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide; and

(ii) converting of 5H-Dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide to oxcarbazepine [I].

According to yet another aspect, there is provided a process for the preparation of oxcarbazepine, comprising the steps of:
(i) reacting the compound of formula [XXIV] and/or its mixture with 5H-dibenzo[b,f] azepine-5-carbonyl bromide with bromine to provide 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride compound of formula [XXV]; and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide; and

(ii) treating 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride compound of formula [XXV] and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide with base in presence of methanol to obtain compound of formula [III]; and

(iii) converting of compound of formula [III] to 10-methoxy-5H-dibenz[b,f]azepine [II]; and

(iv) converting 10-methoxy-5H-dibenz[b,f]azepine [II] to oxcarbazepine [I].

According to yet another aspect, there is provided a process for the preparation of oxcarbazepine, comprising the steps of:
(i) converting of compound of formula [III] to compound of formula [IV]; and

(ii) converting compound of formula [IV] to oxcarbazepine [I].

According to yet another aspect, there is provided a process for the preparation of oxcarbazepine, comprising the steps of:
(i) reacting iminodibenzyl compound of formula [XXI] with triphosgene in presence of solvent to obtain 10,11-Dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride compound of formula [XXII];

(ii) reacting iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate, benzoyl peroxide and solvent at first temperature to obtain compound of formula [XXIII], which is further heated at second temperature to obtain 5H-Dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-Dibenzo[b,f]azepine-5-carbonyl bromide;

(iii) reacting the compound of formula [XXIV] and/or its mixture with 5H-Dibenzo[b,f] azepine-5-carbonyl bromide with liquid bromine to provide 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride compound of formula [XXV] and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide;

(iv) treating compound of formula [XXV] with base in presence of methanol to obtain 10-methoxy-5H-dibenz[b,f]azepine [II]; and

(v) converting of 10-methoxy-5H-dibenz[b,f]azepine [II] to oxcarbazepine [I].

The formyl chlorination of iminodibenzyl compound of formula [XXI] is carried out by reacting with triphosgene in the presence of chlorobenzene at 100°C to reflux temperature preferably at 100-110°C to obtain iminodibenzyl carbonyl chloride compound of formula [XXII].

Conversion of compound of formula [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide to compound of formula [XXV] and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide is carried out using liquid bromine in presence of a solvent at -5 to 30°C; wherein solvent is selected from the group comprising of chlorinated solvents, nitriles, ketones, esters, ethers, amides, dialkylsulfoxide, water or mixtures thereof, preferably chlorinated solvents and more preferably dichloromethane.

Conversion of compound of formula [XXV] and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide to 10-methoxy-5H-dibenz[b,f]azepine [II], according to the present invention comprises reacting [XXV] with HOCN in presence of organic medium, wherein HOCN is generated from cyanate compound which is selected from sodium or potassium cyanate, preferably sodium cyanate. The 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. para-chlorobenzoic acid. Excess molar quantity of the weak acid is preferably used in comparison to 10-methoxy iminostilbene [XXV], in the range of from 2 to 10 molar excess, preferably about 5 to 8 molar excess. Further, the reaction is carried out by 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 and the like.

Conversion of 10-methoxy-5H-dibenz[b,f]azepine [II] to oxcarbazepine [I] is carried out in presence of suitable acid or base in accordance with one preferred embodiment of the present invention, wherein the acid is selected from mineral acids, lower alkane or halogenated lower alkanecarboxylic acids having up to 4 carbon atoms, preferably hydrochloric acid, sulfuric acid, polyphosphoric acid, acetic acid, trichloroacetic acid or trifluoroacetic acid alone or in combination thereof. The 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.

Conversion of compound of formula [XXV] and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide to 10-methoxy iminostilbene compound of formula [II] is carried out by reacting with methanol in presence of a base and solvent at -5 to 5°C to provide compound of formula [III] which is hydrolyzed to give 10-methoxy iminostilbene [II], which may be further purified to obtain pure 10-methoxy iminostilbene.

Radical initiator is selected from the group comprising of benzoyl peroxide, azobisisobutyronitrile, 4,4'-azobis(4-cyanopentanoic acid), acetone peroxide, di-tert-butyl peroxide, 1,1'-dihydroxydicyclohexyl peroxide and the like, preferably benzoyl peroxide.

According to yet another aspect, there is provided a process for the preparation of oxcarbazepine, comprising the steps of:
(i) reacting iminodibenzyl a compound of formula [XXI] with triphosgene in chlorobenzene at 100-110°C to obtain 10,11-Dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride compound of formula [XXII];

(ii) reacting iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate and radical initiator at 65-75°C in chlorobenzene to obtain compound of formula [XXIII], which is further heated 90-100°C to obtain 5H-dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide; and

(iii) converting compound of formula [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide to oxcarbazepine [I].

It has been observed that reaction of iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate and radical initiator at first temperature of about 65-75°C followed by further heating it to temperature of about 90-100°C and not beyond about 100°C is critical to avoid the formation of impurities. Directly raising the reaction temperature to about 90-100°C or beyond about 100°C generate more impurities and reduces the yield.

It is preferable to heat the reaction mixture of iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate and radical initiator at first temperature of about 65-75°C for about 10-15 hours followed by further heating it to temperature of about 90-100°C for about 30-40 hours is critical to avoid the formation of impurities. Further, reaction does not proceed to completion if is not heated to second temperature of about 90-100°C.

Further, a scrubber system was put in place at the back end of the reactor to neutralize any excess phosgene gas produced in the reaction. A peristaltic pump is used to force a solution of NaOH through a column containing raschig rings where it meets the gas from the reactor. A condenser is also built into the system in order to stop the solution overheating and a thermocouple is inserted into the reservoir of NaOH to measure any change in temperature. The residual phosgene of step (i) is removed by scrubbing residual phosgene and/or reaction mass.

The suitable solvent as defined above and/or solvent for recrystallization/purification of oxcarbazepine is selected from the group comprising of alcohols, nitriles, ketones, esters, chlorinated solvents, ethers, amides, dialkylsulfoxide, water or 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 and the like. 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 are selected from the group comprising of diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane and the like. Amide is selected from the group comprising of dimethylformamide, dimethylacetamide, N-methyl formamide, N-methyl pyrrolidine and the like. Dialkylsulfoxide are selected from the group comprising of dimethyl sulfoxide, sulfolane diethyl sulfoxide, dibutyl sulfoxide and the 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.

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 5H-dibenzo[b,f]azepine-5-carbonyl chloride
To a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (200 g) in chlorobenzene , triphosgene (125 g) added at 25-30°C. Resulting mixture was heated to 100-110°C and stirred for 6-8h. Charged benzoyl peroxide (10 g) and sodium bromate (32.4 g) to above resulting mixture at 25-30°C. Heated reaction mass to 65-75°C and added lot-1 of liquid bromine (37.4g) in 3-4h. Maintained reaction mass for 1-2 h at 65-75°C. Added lot-2 of liquid bromine (37.4g) in 3-4h and maintained reaction mass for 1-2 h at 65-75°C. Added lot-3 of liquid bromine (37.4g) in 3-4h and maintained reaction mass for 1-2 h at 65-75°C. Heated reaction mass for 90-100°C and stirred for 40h, after completion of reaction cooled reaction mass at 75-80°C and separated layers. Cooled organic layer to 25-30°C and washed with aqueous solution of sodium metabisulphite (400 mL, 5.0% w/v) followed by water wash (400 mL). Organic layer was distilled under vacuum at 60-65°C up to reaction mass (~1-2V). Cooled residual mass to 25-30°C and charged methanol. Heated resulting mixture to 55-60°C and maintained for 1-2 h at 55-60°C, cooled reaction mass to 25-30°C in 3-4 h and further cooled to 15-20°C in 1-2h, stirred reaction mixture for 30-40 min at 15-20°C. Filtered the material at 15-20°C and wet material washed with chilled methanol. Wet material charged to mixture of methanol (600mL) and chlorobenzene (50 mL) at 25-30°C. Heated resulting mixture to 55-60°C and maintained for 1-2 h at 55-60°C, cooled reaction mass to 25-30°C in 3-4 h and further cooled to 15-20°C in 1-2h, stirred reaction mixture for 30-40 min at 15-20°C. Filtered the material at 15-20°C and wet material washed with chilled methanol followed by DM water. Dried material at 75-80°C under vacuum to obtained titled compound, 5H-dibenzo[b,f]azepine-5-carbonyl chloride. (Dry weight: 232.20 g, HPLC purity: 99.5%, Yield: 88.66%)

Example 3: Preparation of 5H-dibenzo[b,f]azepine-5-carbonyl chloride
To a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (200 g) in chlorobenzene, triphosgene (125 g) added at 25-30°C. Resulting mixture heated to 100-110°C and stirred for 6-8h and removed residual phosgene through scrubbing. The reaction mass was further scrubbed at about 100-110°C for 5-7h to remove the residual phosgene gas and then cooled to 25-30°C. Then 46-48% caustic lye (1.92 g) solution was charged to reaction mass at 25-30°C and stirred resulting mixture for 30-60 min at 25-30°C. Charged benzoyl peroxide (10 g) and sodium bromate (32.4g) to above resulting mixture at 25-30°C. Heated reaction mass to 65-75°C and added lot-1 of liquid bromine (37.4g) in 3-4h. Maintained reaction mass for 1-2 h at 65-75°C. Added lot-2 of liquid bromine (37.4g) in 3-4h and maintained reaction mass for 1-2 h at 65-75°C. Added lot-3 of liquid bromine (37.4g) in 3-4h and maintained reaction mass for 1-2 h at 65-75°C. Heated reaction mass for 90-100°C and stirred for 40h, after completion of reaction cooled reaction mass at 75-80°C and separated layers. Cooled organic layer to 25-30°C and washed with aqueous solution of sodium metabisulphite (400 mL, 5.0% w/v) followed by water wash (400 mL). Organic layer was distilled under vacuum at 60-65°C up to reaction mass (~1-2V). Cooled residual mass to 25-30°C and charged methanol (600 mL). Heated resulting mixture to 55-60°C and maintained for 1-2 h at 55-60°C, cooled reaction mass to 25-30°C in 3-4 h and further cooled to 15-20°C in 1-2h, stirred reaction mixture for 30-40 min at 15-20°C. Filtered the material at 15-20°C and wet material washed with chilled methanol. Wet material charged to mixture of methanol (600mL) and chlorobenzene (50 mL) at 25-30°C. Heated resulting mixture to 55-60°C and maintained for 1-2 h at 55-60°C, cooled reaction mass to 25-30°C in 3-4 h and further cooled to 15-20°C in 1-2h, stirred reaction mixture for 30-40 min at 15-20°C. Filtered the material at 15-20°C and wet material washed with chilled methanol followed by DM water. Dried material at 75-80°C to obtain 5H-dibenzo[b, f] azepine-5-carbonyl chloride. (Dry weight: 232.10 g, HPLC purity: 99.5%, Yield: 88.62%)

Example 4: Preparation of 5H-dibenzo[b,f]azepine-5-carbonyl chloride
To a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (200 g) in chlorobenzene solvent, triphosgene (125 g) added at 25-30°C. Resulting mixture heated to 100-110°C and stirred for 6-8h. Charged benzoyl peroxide (10 g) and sodium bromate (32.4 g) to above resulting mixture at 25-30°C. Heated reaction mass to 65-75°C and added lot-1 of liquid bromine (37.4g) in 3-4h. Maintained reaction mass for 1-2 h at 65-75°C. Added lot-2 of liquid bromine (37.4g) in 3-4h and maintained reaction mass for 1-2 h at 65-75°C. Added lot-3 of liquid bromine (37.4g) in 3-4h and maintained reaction mass for 1-2 h at 65-75°C. Heated reaction mass for 90-100°C and stirred for 40h, after completion of reaction cooled reaction mass at 75-80°C and separated layers. Cooled organic layer to 25-30°C and washed with aqueous solution sodium metabisulphite (400 mL, 5.0% w/v) followed by water wash (400 mL). Organic layer distilled under vacuum at 60-65°C up to stirable reaction mass (~1-2V). Cooled residual mass to 25-30°C and charged methanol. Heated resulting mixture to 55-60°C and maintained for 1-2 h at 55-60°C, cooled reaction mass to 25-30°C in 3-4 h and further cooled to 15-20°C in 1-2h, stirred reaction mixture for 30-40 min at 15-20°C. Filtered the material at 15-20°C and wet material washed with chilled methanol. Wet material charged to mixture of methanol (600mL) and chlorobenzene (50 mL) at 25-30°C. Heated resulting mixture to 55-60°C and maintained for 1-2 h at 55-60°C, cooled reaction mass to 25-30°C in 3-4 h and further cooled to 15-20°C in 1-2h, stirred reaction mixture for 30-40 min at 15-20°C. Filtered the material at 15-20°C and wet material washed with chilled methanol followed by DM water. Dried material at 75-80°C under vacuum to obtained titled compound, 5H-dibenzo[b,f]azepine-5-carbonyl chloride. (Dry weight: 232.20 g, HPLC purity: 99.5%, Yield: 88.66%)

Example 5: Preparation of 10-methoxy-5H-dibenz[b,f] azepine:
To solution of 5H-dibenzo[b,f]azepine-5-carbonyl chloride (150 g) in dichloromethane cooled to -5 to 5°C and added solution of liquid bromine (107g) in dichloromethane (150 mL) at -5 to 5°C. Stirred reaction mass for 1-2 h at -5 to 5°C. Charged solution of sodium metabisulphite (18.0 g) in DM water (750 mL) at 25-30 °C, stirred resulting mixture for 15-20 min at 25-30°C, settled reaction mass for 15-20min and separated the layers. dichloromethane layer washed with DM water followed by solution of sodium bicarbonate in DM water at 25-30°C. Distilled dichloromethane atmospherically at 38-40°C followed by applying vacuum to remove traces of dichloromethane at 38-40°C. Cooled residual mass to 25-30°C and charged toluene solvent (1500 mL), cooled resulting mass to -5 to 5°C, charged potassium hydroxide flakes (218 g) and sodium hydroxide flakes (133 g) at -5 to 5°C. Stirred reaction mass for 10-15 min at -5 to 5°C and slowly added methanol (450 mL) at -5 to 5°C by maintaining temperature -5 to 5°C, stirred resulting mixture for 30-45 min at -5 to 5°C. Heated resulting mixture at 80-90°C and stirred reaction mass for 24-30 h at 80-90°C, after completion of reaction cooled reaction mass to 25-30°C, slowly Charged DM water (1200 mL) at 25-30°C and stirred reaction mass for 30 min, settled for 15-20 min and separated layers, Toluene layer was washed with DM water. Charged activated carbon to toluene layer at 25-30°C, heated resulting mixture to 45-50°C and stirred for 1-2 h at 45-50°C, cooled reaction mass to 25-30°C. Filtered the resulting mixture at 25-30°C through hyflo bed and hyflo bed washed with toluene (75 mL), collected filtrate heated to 60-65°C. Distilled toluene at 60-65°C up to stirable reaction mass, cooled reaction mass to 25-30°C. Charged IPA (600 mL) to residue mass at 25-30°C and heated to 80-85°C (reflux) to get clear solution and maintained for 30 min at reflux. Cooled reaction mass to 25-30°C and maintained for 8 h at 25-30°C and further cooled reaction mass to 0-5°C and maintained for 2 h at 0-5°C. Filtered the material at 0-5°C and wet material washed with IPA (75mL, precooled to 0-5°C). Dried the wet material at 50-55ºC for 6-8h under vacuum to obtained titled compound, 10-methoxy-5H-dibenz[b,f]azepine (Dry weight: 112 g, HPLC purity: 99.96%, Yield: 85.51%)

Example 6: Preparation of 10-methoxy-5H-dibenz[b,f] azepine:
To Solution of 5H-dibenzo[b,f]azepine-5-carbonyl chloride (150 g) in dichloromethane solvent cooled to -5 to 5°C and added solution of liquid bromine (107g) in dichloromethane (150 mL) at -5 to 5°C. Stirred reaction mass for 1-2 h at -5 to 5°C, charged solution of sodium metabisulphite (18.0 g) in DM water (750 mL) at 25-30 °C, stirred resulting mixture for 15-20 min at 25-30°C, settled reaction mass for 15-20min and separated layers. Dichloromethane layer washed with DM water ( 450 mL) followed by solution of sodium bicarbonate (18.0 g) in DM water (300 mL) and DM water (450 mL) at 25-30°C. Distilled out dichloromethane and cooled the residual mass to 25-30°C and charged toluene solvent (1500 mL), cooled resulting mass to -5 to 5°C, charged potassium hydroxide flakes and sodium hydroxide flakes at -5 to 5°C. Stirred reaction mass for 10-15 min at -5 to 5°C and slowly added methanol (450 mL) at -5 to 5°C by maintaining temperature -5 to 5°C, stirred resulting mixture for 30-45 min at -5 to 5°C. Heated resulting mixture at 80-90°C and stirred reaction mass for 24-30 h at 80-90°C, progress of reaction monitored by HPLC after completion of reaction cooled reaction mass to 25-30°C, slowly Charged DM water at 25-30°C and stirred reaction mass for 30 min, settled for 15-20 min and separated layers, Toluene layer washed with DM water. Charged activated carbon (3 g) to toluene layer at 25-30°C, heated resulting mixture to 45-50°C and stirred for 1-2 h at 45-50°C, cooled reaction mass to 25-30°C. Filtered the resulting mixture at 25-30°C through hyflo bed and hyflo bed washed with toluene (75 mL), collected filtrate heated to 60-65°C. Distilled toluene at 60-65°C under vacuum up to stirable reaction mass (~1.5-2.0 V), cooled reaction mass to 25-30°C. Charged IPA (600 mL) to residue mass at 25-30°C and heated to reflux to get clear solution and maintained for 30 min at reflux. Cooled reaction mass to 25-30°C and maintained for 8 h at 25-30°C and further cooled reaction mass to 0-5°C and maintained for 2 h at 0-5°C. Filtered the material at 0-5°C and wet material washed with IPA. Dried the wet material at 50-55ºC for 6-8h under vacuum to obtain 10-methoxy-5H-dibenz[b,f]azepine (Dry weight: 112.2 g, HPLC purity: 99.96%, Yield: 85.66%)

Example 7: Preparation of 10-oxo-10,11-dihydro-5H-dibenz [b,f]azepine -5-caboxamide (Oxcarbazepine):
Charge toluene and DM water, stir for 15min at 25-30oC, settle for 15min, separate the bottom aq. layer, heat the reaction mass to reflux and remove water by azeotropically till temperature reaches to not less than 110°C, cooled reaction mixture to 25-30oC, charged 10-methoxy-5H-dibenz[b,f]azepine (100g) and heated the reaction mass and distilled out 50mL of toluene under atmospheric pressure. Cooled the reaction mass and charged sodium cyanate (109.3g) at 30-40oC. Heated the reaction mass to 85-95°C. Charged benzoic acid (205.4g) into reactor at 85-95°C in lot wise, maintained the reaction mass at 85-95°C for about 180min. Cooled the reaction mass to 70-75°C. Cooled the reaction mass to 40-45oC, slowly added solution of sodium hydroxide in DM water at 40-45oC, cooled resulting mixture to 25-30oC and maintained for about 10-12 h. Cooled the mass to 0-10oC and maintain the reaction mass for 6-7 h at 0-10°C. Filtered the mass & washed with toluene and dried material to obtained 10-methoxy carbamazepine i.e. Compound of Formula [IV].

To a solution of 10-methoxy carbamazepine in methanol (485 mL) and DM water (100mL), stirred for 5-10min. Heated the mass to 65-75oC (reflux) and maintain for about 30min. Distilled out methanol till the volume of reaction mass reaches to 3-3.6 volume in reactor. Charged DM water (300mL) and conc. HCl (24.78g) into reactor at NLT 55°C. Heated the reaction mass to 75-80°C and maintained the reaction mass for about 6-12h at 75-80°C. Cooled the reaction mixture to 25-30oC and maintained the mass for about 2h under stirring at 25-30°C. Filtered the material and washed with 5% sodium bicarbonate (15g) solution in DM water (300 mL) followed by DM water (100 mL) and solution of TEA (2 mL) in methanol (100 mL). Dried the material to obtain oxcarbazepine. (Dry weight: 94.0 g, HPLC purity: 99.9%, Yield: 83.19%)

Example 8: Purification of crude 10-oxo-10, 11-dihydro-5H-dibenz [b,f]azepine -5-caboxamide (Oxcarbazepine):
Charged hyflo (5g) to a mixture of methanol (1500 mL) and dichloromethane (1500mL) and filtered the mass, filtrate passed through sodium carbonate (~0.5g) and checked the pH of filtrate. (Limit of pH: 9.5-10.5). Charged filtrate (2800 mL) and crude oxcarbazepine (100 g), stirred resulting mixture for 15 min, charged activated carbon to resulting mixture and heated the reaction mass to reflux. Filtered the mass and washed with mixture of methanol and dichloromethane. Distilled out solvent mixture, cooled reaction mass to 25-30°C, further cooled to 0-5°C. Filtered the material and washed with methanol. Dried material under vacuum at 50-60°C to obtained pure oxcarbazepine (Dry weight: 90.0 g, HPLC purity: 99.98%, Yield: 90.0%)
,CLAIMS:1. A process for the preparation of Oxcarbazepine [I], comprising the steps of:

(i) reacting iminodibenzyl compound of formula [XXI] with triphosgene in presence of solvent to obtain 10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride compound of formula [XXII];

(ii) reacting compound of formula [XXII] with bromine in presence of sodium bromate, radical initiator and solvent at first temperature to obtain compound of formula [XXIII], which is further heated at second temperature to obtain 5H-dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide;

(iii) converting of 5H-dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide to Oxcarbazepine [I].

2. The process as claimed in claim 1, wherein reaction in step (i) with triphosgene is carried out at a temperature of 100-110°C.

3. The process as claimed in claim 1, wherein the first temperature in step (ii) is 65-75°C and second temperature in step (ii) is 90-100°C.

4. The process as claimed in claim 1, wherein solvent in step (i) and (ii) is chlorobenzene.

5. The process as claimed in claim 1, wherein in step (ii) reaction of iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate and radical initiator is performed at first temperature of 65-75°C for 10-15 hours followed by further heating it to temperature of 90-100°C for 30-40 hours.

6. The process as claimed in claim 1, wherein radical initiator is selected from the group comprising of benzoyl peroxide, azobisisobutyronitrile, 4,4'-azobis (4-cyanopentanoic acid), acetone peroxide, di-tert-butyl peroxide and 1,1'-dihydroxydicyclohexyl peroxide.

7. The process as claimed in claim 1, process for the preparation of oxcarbazepine [I], comprising the steps of:
(i) reacting the compound of formula [XXIV] and/or its mixture with 5H-dibenzo[b,f] azepine-5-carbonyl bromide with bromine to provide 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride compound of formula [XXV]; and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide; and

(ii) treating 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride compound of formula [XXV] and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide with base in presence of methanol to obtain 10-methoxy-5H-dibenz[b,f]azepine [II]; and

(iii) converting of 10-methoxy-5H-dibenz[b,f]azepine [II] to oxcarbazepine [I].

a. The process as claimed in claim 7, wherein in step (i) reaction is carried out at -5 to 30°C in presence of dichloromethane solvent.

9. The process as claimed in claim 1, for the preparation of oxcarbazepine [I], comprising the steps of:

(i) treating iminodibenzyl a compound of formula [XXI] with triphosgene in presence of solvent to obtain 10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride compound of formula [XXII];

(ii) treating iminodibenzyl carbonyl chloride compound of formula [XXII] with liquid bromine in presence of sodium bromate and solvent at a first temperature to obtain compound of formula [XXIII], which is further heated at a second temperature to obtain 5H-Dibenzo[b,f]azepine-5-carbonyl chloride [XXIV] and/or its mixture with 5H-Dibenzo[b,f]azepine-5-carbonyl bromide;

(iii) treating compound of formula [XXIV] and/or its mixture with 5H-dibenzo[b,f]azepine-5-carbonyl bromide with liquid bromine to provide 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl chloride compound of formula [XXV]; and/or its mixture with 10,11-dibromo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-caronyl bromide;

(iv) treating compound of formula [XXV] with base in presence of methanol to obtain 10-methoxy-5H-dibenz[b,f]azepine [II]; and

(v) converting of 10-methoxy-5H-dibenz[b,f]azepine [II] to oxcarbazepine
wherein formation of 5H-dibenz[b,f]azepine [XXIV] starting from iminodibenzyl [XXI] and formation of 10-methoxy-5H-dibenz[b,f]azepine [II] starting from 5H-dibenz[b,f] azepine [XXIV] are carried out in-situ without isolation of any intermediate compound.

10. The process as claimed in claim 1, wherein residual phosgene of step (i) is removed by scrubbing residual phosgene and/or reaction mass.