Preparation method of oxcarbazepine

Abstract

The invention discloses a preparation method of oxcarbazepine, and belongs to the technical field of drug synthesis, 2-bromophenylacetyl chloride and N-phenyl cyanamide are subjected to a Friedel-Crafts reaction, and the temperature is controlled at 0-20 DEG C, so that the occurrence of side reactions can be effectively reduced, and the conversion rate of raw materials can be improved. According to the preparation method disclosed by the invention, only a palladium catalyst needs to be used in the synthesis process of the 10-oxo-10, 11-dihydro-5H-dibenzo [b, f] azepine-5-carbonitrile, so that the synthesis cost is effectively reduced, and the post-treatment process is simple; in the hydrolysis reaction, water or dichloromethane is used as a solvent, and 10-oxo-10, 11-dihydro-5H-dibenzo [b, f] aza-5-formamide is obtained under the catalysis of an acidic reagent. The preparation method provided by the invention has the advantages of easily available raw materials, low cost, mild process conditions and simple post-treatment process, and is more beneficial to realization of industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of drug synthesis, and in particular to a method for preparing oxcarbazepine. Background Art

[0002] Oxcarbazepine (OCBZ) is a new anti-epileptic drug with numerous synthesis reports, mainly including the iminostilbene method, the carbamazepine method, and the 10-methoxy-iminostilbene method.

[0003] Route 1 is a method for synthesizing oxcarbazepine reported by Zhang Shengjian et al., which belongs to the iminostilbene method. 5H-dibenzo[b,f]azepine-5-carbonyl chloride is used as the raw material. OCBZ is obtained through halogenation, aminolysis, and hydrolysis. The synthetic route is as follows: , the halogen raw materials used in this method are not easy to purchase.

[0004] Route 2: Diao Wenrui et al. used 10,11-dihydro-5H-dibenzo[b,f]azepine to react with triphosgene to obtain 10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride, which was then subjected to a one-pot double bromination reaction with dibromohydantoin in the presence of a free radical initiator, benzoyl peroxide, followed by high-temperature dehydrobromination to obtain 10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride. The synthetic route is as follows: This method uses triphosgene as the reaction condition, which is relatively dangerous and has a yield of only 39%.

[0005] Route 3 is an invention patent with publication number DE2246842A1. Carbamazepine is used as a raw material. Carbamazepine is first oxidized to generate 10,11-epoxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide, which is then rearranged to obtain oxcarbazepine. The synthetic route is as follows: The raw material in the above synthesis method is carbamazepine, which is relatively expensive.

[0006] The synthetic reaction route of oxcarbazepine provided in Scheme 4 is: (See, e.g., Tetrahedron, 2007, 63, 690-702), wherein the multi-step reaction requires the use of a palladium catalyst, which is expensive and complex to operate. Summary of the Invention

[0007] The present invention provides a method for preparing oxcarbazepine, which effectively solves the technical problems in the existing oxcarbazepine synthesis process, such as the difficulty in obtaining raw materials, long reaction time, complicated post-processing, high preparation cost and low oxcarbazepine yield. At the same time, a method for preparing oxcarbazepine is provided, which can effectively reduce production costs and improve product yield.

[0008] The object of the present invention is to provide a method for preparing oxcarbazepine, comprising the following steps: Using 2-bromophenylacetyl chloride of Formula 1 and N-phenylcyanamide of Formula 2 as raw materials, a Friedel-Crafts reaction occurs at 0-20°C under the catalysis of a Lewis acid, whereby the chlorine atom in 2-bromophenylacetyl chloride replaces the hydrogen atom at the ortho position of cyanamide to obtain N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide of Formula 3.

[0009] N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide of formula 3 is used as a raw material, a phosphine ligand is added, and a Buchwald-Hartwig reaction is carried out at 110°C to 130°C under the action of a palladium catalyst and an alkaline reagent. The amine in N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide undergoes a cross-coupling reaction with an aromatic halide to form a CN bond to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]Azoline-5-carbonitrile.

[0010] 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] azepine-5-carbonitrile as raw material, water or dichloromethane as solvent, at 40 ℃ ~ 100 ℃, acidic reagent catalyzed hydrolysis reaction to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] Azaquinone-5-carboxamide, namely oxcarbazepine, has a synthetic route as follows: .

[0011] As a preferred embodiment, the molar ratio of 2-bromophenylacetyl chloride to N-phenylcyanamide is 1:1 to 1.2.

[0012] As a preferred embodiment, the Lewis acid is ferric chloride or aluminum chloride, and the molar ratio of the 2-bromophenylacetyl chloride to the Lewis acid is 1:1-3.

[0013] As a preferred embodiment, the molar ratio of N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide to the phosphine ligand is 1:0.1~0.3, and the molar ratio of N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide, the palladium catalyst and the alkaline reagent is 1:0.1~0.3:5~8.

[0014] As a preferred embodiment, the phosphine ligand is 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 1,1'-bis(diphenylphosphino)ferrocene or 4,5-bisdiphenylphosphino-9,9-dimethylxanthene.

[0015] As a preferred embodiment, the alkaline agent is cesium carbonate, sodium tert-butoxide or potassium phosphate; the palladium catalyst is palladium acetate, tris(dibenzylidene-BASE acetone)dipalladium or tetrakistriphenylphosphine palladium.

[0016] As a preferred embodiment, the 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]The molar ratio of azepine-5-carbonitrile to the acidic reagent is 1:6~8.

[0017] As a preferred embodiment, the acidic reagent is hydrochloric acid with a mass concentration of 36% or sulfuric acid with a mass concentration of 84%.

[0018] As a preferred embodiment, the Friedel-Crafts reaction time is 6 h to 7 h, the Buchwald-Hartwig reaction time is 5 h to 8 h, and the hydrolysis reaction time is 2 h to 3 h.

[0019] As a preferred embodiment, during the Friedel-Crafts reaction, dichloromethane is used as the solvent. After the reaction is completed for 6 to 7 hours, 0.5 M to 1 M hydrochloric acid is used to remove excess Lewis acid to obtain an aqueous phase. The aqueous phase is extracted with dichloromethane, and the organic phase is washed and dried, and the solvent is removed to obtain N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide.

[0020] As a preferred embodiment, the Buchwald-Hartwig reaction is carried out using toluene, xylene or N,N-dimethylformamide as a solvent. After the reaction is completed for 5 to 8 hours, dichloromethane is used for extraction. The organic phase is washed with deionized water and saturated brine, dried, the solvent is removed, and column chromatography is performed to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]Azoline-5-carbonitrile.

[0021] As a preferred embodiment, during the hydrolysis reaction, after the reaction is completed for 2h to 3h, a reaction solution is obtained, the reaction solution is extracted with ethyl acetate, the organic phase is washed with deionized water and saturated brine, dried, and the solvent is removed to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]Azepine-5-carboxamide.

[0022] As a preferred embodiment, the preparation method of N-phenylcyanamide comprises the following steps: using aniline and cyanogen bromide as raw materials, a nucleophilic substitution reaction occurs in acetonitrile or anisole solvent at 50° C. to 70° C. in an alkaline solution to obtain N-phenylcyanamide.

[0023] As a preferred embodiment, the alkaline solution is potassium carbonate, sodium carbonate, sodium hydride or sodium hydroxide; and the molar ratio of aniline to the alkaline solution is 1:1-3.

[0024] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a preparation method of oxcarbazepine. In the present invention, 2-bromophenylacetyl chloride and N-phenylcyanamide are subjected to a Friedel-Crafts reaction, and the temperature is controlled at 0°C to 20°C, which can effectively reduce the occurrence of side reactions and improve the conversion rate of raw materials. In addition, the process conditions are mild, the operation safety is high, and it is more conducive to industrial production. In the present invention, only a palladium catalyst is required in the synthesis process of 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile, thereby effectively reducing the synthesis cost and simplifying the post-processing process. During the hydrolysis reaction, water or dichloromethane is used as a solvent and catalyzed by an acidic reagent to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile. b , f ] Azaquinone-5-carboxamide, the raw materials of the method of the present invention are easily available and low in cost, the synthesis process conditions are mild, and the operation safety is high. DETAILED DESCRIPTION

[0025] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention is further described below with reference to specific examples, but the examples are not intended to limit the present invention. The following experimental and detection methods are conventional methods unless otherwise specified; the reagents and raw materials are commercially available unless otherwise specified.

[0026] In view of the technical problems of the existing synthesis method of oxcarbazepine, such as difficult to obtain raw materials, long reaction time, complicated post-processing, high preparation cost and low oxcarbazepine yield, the present invention provides a preparation method of oxcarbazepine.

[0027] The technical solution of the present invention is described in detail below.

[0028] The present invention provides a method for preparing oxcarbazepine, comprising the following steps: S1. Using 2-bromophenylacetyl chloride of Formula 1 and N-phenylcyanamide of Formula 2 as raw materials, a Friedel-Crafts reaction occurs at 0°C to 20°C under Lewis acid catalysis, whereby the chlorine atom in 2-bromophenylacetyl chloride replaces the hydrogen atom at the ortho position of cyanamide to obtain N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide of Formula 3. Regarding the aforementioned reaction temperature of 0°C to 20°C, if the reaction temperature is below 0°C, the reaction of the raw materials will be incomplete. If the reaction temperature is above 20°C, side reactions will occur to generate impurities, resulting in a reduced product yield.

[0029] S2, using N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide of formula 3 as a raw material, adding a phosphine ligand, and carrying out a Buchwald-Hartwig reaction at 110°C to 130°C under the action of a palladium catalyst and an alkaline reagent, the amine in N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide undergoes a cross-coupling reaction with an aromatic halide to form a CN bond, thereby obtaining an N-arylation product of the amine, thereby obtaining 10-oxo-10,11-dihydro-5H-dibenzo[ b , f Regarding the reaction temperature of 110°C to 130°C, when the reaction temperature is lower than 110°C, the raw materials are not completely reacted, the reaction time is long, and the yield is low; when the reaction temperature is higher than 130°C, the reaction by-products increase and the yield of the product decreases. The reaction mechanism is as follows: .

[0030] S3, 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] azepine-5-carbonitrile as raw material, at 40 ℃ ~ 100 ℃, acidic reagent catalyzed hydrolysis reaction to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] Azaquinone-5-carboxamide, namely oxcarbazepine, has a synthetic route as follows: The temperature of the hydrolysis reaction is 40°C to 100°C. When the reaction temperature is lower than 40°C, the hydrolysis reaction time is prolonged and the raw materials are not completely reacted. When the reaction temperature is higher than 100°C, by-products are easily generated, making post-processing difficult.

[0031] In the process of preparing N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide of formula 3, the molar ratio of 2-bromophenylacetyl chloride to N-phenylcyanamide is 1:1~1.2. When the molar amount of N-phenylcyanamide is less than 1 as defined herein, it will cause N-phenylcyanamide to be difficult to react completely, resulting in a low reaction conversion rate; when the molar amount of N-phenylcyanamide is greater than 1.2 as defined herein, it will lead to increased side reactions, the generation of polysubstituted impurities, and reduced reaction selectivity.

[0032] To obtain a product of higher purity, the Lewis acid is ferric chloride or aluminum chloride, and the molar ratio of 2-bromophenylacetyl chloride to the Lewis acid is 1:1 to 3. When the molar amount of the Lewis acid is less than 1, as defined herein, the reaction rate and yield decrease, and side reactions are likely to occur. When the molar amount of the Lewis acid is greater than 3, the chlorine atoms in the 2-bromophenylacetyl chloride excessively replace the hydrogen atoms ortho to the cyanamide, resulting in reduced selectivity and difficult post-processing.

[0033] It should be noted that the molar ratio of the N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide to the phosphine ligand is 1:0.1~0.3, and the molar ratio of the N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide, the palladium catalyst and the alkaline reagent is 1:0.1~0.3:5~8.

[0034] In order to further improve the catalytic ability of the palladium catalyst, the phosphine ligand is 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 1,1'-bis(diphenylphosphino)ferrocene or 4,5-bisdiphenylphosphino-9,9-dimethylxanthene. The phosphine ligand mainly acts on the palladium catalyst to improve the catalytic ability of the palladium catalyst and make the reaction easier to proceed.

[0035] It should be noted that the alkaline reagent used in the present invention is cesium carbonate, sodium tert-butoxide or potassium phosphate; the palladium catalyst used is palladium acetate, tris(dibenzylidene-BASE acetone)dipalladium or tetrakistriphenylphosphine palladium.

[0036] In order to improve the reaction process of the hydrolysis reaction and increase the product yield, the 10-oxo-10,11-dihydro-5H-dibenzo[ b , f The molar ratio of azepine-5-carbonitrile to the acidic reagent is 1:6~8. The acidic reagent is 36% concentrated hydrochloric acid or 84% concentrated sulfuric acid.

[0037] In the present invention, in order to maximize the yield of the product in each step, the time of the Friedel-Crafts reaction is limited to 6 h to 7 h, the time of the Buchwald–Hartwig reaction is limited to 5 h to 8 h, and the time of the hydrolysis reaction is limited to 2 h to 3 h.

[0038] In order to further improve the yield and purity of the product N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide, the Friedel-Crafts reaction is carried out using dichloromethane as a solvent. After the reaction is completed, 0.5M to 1M hydrochloric acid is used to remove excess Lewis acid to obtain an aqueous phase. The aqueous phase is extracted with dichloromethane, and the organic phase is washed and dried, and then the solvent is removed to obtain N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide.

[0039] In order to improve the product 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] yield and purity of azepine-5-carbonitrile, in the Buchwald-Hartwig reaction, toluene, xylene or N, N-dimethylformamide is used as solvent, after the reaction is completed, dichloromethane is used for extraction, the organic phase is washed with deionized water and saturated brine, dried, the solvent is removed, and column chromatography is performed to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]Azoline-5-carbonitrile.

[0040] In order to improve the yield and purity of the product oxcarbazepine, the hydrolysis reaction is carried out using water or dichloromethane as a solvent. After the reaction is completed, a reaction solution is obtained, which is extracted with ethyl acetate. The organic phase is washed with deionized water and saturated brine, dried, and the solvent is removed to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]Azepine-5-carboxamide.

[0041] The preparation method of the raw material N-phenylcyanamide used in the present invention comprises the following steps: using aniline and cyanogen bromide as raw materials, a nucleophilic substitution reaction occurs in acetonitrile or anisole solvent at 50°C to 70°C in an alkaline solution to obtain N-phenylcyanamide. The alkaline solution is potassium carbonate, sodium carbonate, sodium hydride or sodium hydroxide; the molar ratio of aniline to the alkaline solution is 1:1 to 3. When the molar amount of the alkaline solution is less than 1 as defined herein, it will be difficult for the aniline to be completely hydrogenated, resulting in difficulty in the complete reaction and a low conversion rate. When the molar amount of N-phenylcyanamide is greater than 3 as defined herein, increasing the amount of the alkaline solution has no significant effect on the yield, and further increasing the amount of the alkaline solvent is inappropriate in terms of cost.

[0042] The present invention will now be further described with reference to specific embodiments and comparative examples.

[0043] Example 1 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), potassium carbonate (2.07 g, 0.016 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 60°C for 14 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 65%.

[0044] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.51 g, 4.3 mmol), AlCl3 (0.68 g, 5.16 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 20°C for 6 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the starting materials were completely reacted to obtain a reaction solution. 0.5 M dilute hydrochloric acid was added to the reaction solution under an ice-water bath to adjust the pH of the reaction solution to 7. The solution was extracted with dichloromethane (20 mL). The operation was repeated once. The organic phase was washed with water (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The organic phase was purified by column chromatography with a gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 65%.

[0045] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.59 g, 0.95 mmol), potassium phosphate (7.07 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 130°C and monitored by TLC (petroleum ether / ethyl acetate = 2 / 1). After the raw materials were completely reacted, the reaction solution was cooled to room temperature and diluted with 50 mL of dichloromethane. 100 mL of water was added, and the reaction solution was shaken, separated, and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The solution was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 61%.

[0046] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 36% hydrochloric acid (2.16 g, 27.14 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 40°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 62%.

[0047] Example 2 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), potassium carbonate (4.146 g, 0.03 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 60°C for 14 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a 60% yield.

[0048] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.51 g, 4.3 mmol), AlCl3 (1.15 g, 8.6 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 10°C for 8 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the starting materials were completely reacted to obtain a reaction solution. 0.5 M dilute hydrochloric acid was added to the reaction solution under an ice-water bath to adjust the pH of the reaction solution to 7. The solution was extracted with dichloromethane (20 mL). The operation was repeated once. The organic phase was washed with water (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The organic phase was purified by column chromatography with a gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 50%.

[0049] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.59 g, 0.95 mmol), potassium phosphate (7.07 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 110°C and monitored by TLC (petroleum ether / ethyl acetate = 2 / 1). After the raw materials were completely reacted, the reaction solution was cooled to room temperature and diluted with 50 mL of dichloromethane. 100 mL of water was added, and the reaction solution was shaken, separated, and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The mixture was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 55%.

[0050] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 36% hydrochloric acid (2.16 g, 27.14 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 60°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 67%.

[0051] Example 3 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), potassium carbonate (1.38 g, 0.01 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 60°C for 17 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 58%.

[0052] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.51 g, 4.3 mmol), FeCl3 (1.39 g, 8.6 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 10°C for 9 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the starting materials were completely reacted to obtain a reaction solution. The reaction solution was filtered, and the filtrate was extracted with dichloromethane (40 mL). The operation was repeated once. The organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The organic phase was purified by column chromatography with gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 47%.

[0053] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-bis(diphenylphosphino)ferrocene (0.53 g, 0.95 mmol), potassium phosphate (7.07 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, stirred, and heated. The oil bath temperature was set to 130°C. TLC (petroleum ether / ethyl acetate = 2 / 1) was monitored. After the raw materials were completely reacted, the reaction solution was cooled to room temperature, and 50 mL of dichloromethane was added to the reaction solution to dilute it. 100 mL of water was then added, shaken, and the layers were separated and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The mixture was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 62%.

[0054] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 84% sulfuric acid (3.16 g, 27.14 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 50°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 64%.

[0055] Example 4 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), sodium hydroxide (0.60 g, 0.015 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 60°C for 14 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 55%.

[0056] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.51 g, 4.3 mmol), FeCl3 (0.69 g, 4.3 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 20°C for 6 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the raw materials were completely reacted to obtain a reaction liquid. The reaction liquid was filtered, and the filtrate was extracted with dichloromethane (40 mL). The operation was repeated once. The organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The organic phase was purified by column chromatography with gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 45%.

[0057] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.59 g, 0.95 mmol), potassium phosphate (7.07 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 120°C and monitored by TLC (petroleum ether / ethyl acetate = 2 / 1). After the raw materials were completely reacted, the reaction solution was cooled to room temperature and diluted with 50 mL of dichloromethane. 100 mL of water was then added, and the reaction solution was shaken, separated, and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The solution was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 58%.

[0058] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 36% hydrochloric acid (2.16 g, 27.14 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 70°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 68%.

[0059] Example 5 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), sodium carbonate (1.59 g, 0.015 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 60°C for 14 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 55%.

[0060] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.59 g, 5 mmol), AlCl3 (1.33 g, 10 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 0°C for 12 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the starting materials were completely reacted to obtain a reaction solution. 0.5 M dilute hydrochloric acid was added to the reaction solution under an ice-water bath to adjust the pH of the reaction solution to 7. The solution was extracted with dichloromethane (40 mL) and the operation was repeated once. The organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The organic phase was purified by column chromatography with a gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 54%.

[0061] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.59 g, 0.95 mmol), cesium carbonate (10.83 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, stirred, and heated. The oil bath temperature was set to 130°C. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) was performed. After the raw materials were completely reacted, the reaction solution was cooled to room temperature, and 50 mL of dichloromethane was added to the reaction solution to dilute it. 100 mL of water was then added, shaken, and the layers were separated and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The mixture was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 63%.

[0062] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 36% hydrochloric acid (3.46 g, 34.16 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 50°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, in a yield of 64%.

[0063] Example 6 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), sodium hydroxide (0.60 g, 0.015 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 50°C for 18 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 65%.

[0064] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.51 g, 4.3 mmol), FeCl3 (1.39 g, 8.6 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 0°C for 11 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the starting materials were completely reacted to obtain a reaction solution. 0.5 M dilute hydrochloric acid was added to the reaction solution under an ice-water bath to adjust the pH of the reaction solution to 7. The solution was extracted with dichloromethane (20 mL) and the operation was repeated once. The organic phase was washed with water (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The organic phase was purified by column chromatography with a gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 52%.

[0065] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-bis(diphenylphosphino)ferrocene (0.53 g, 0.95 mmol), potassium phosphate (7.07 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, stirred, and heated. The oil bath temperature was set to 120°C. TLC (petroleum ether / ethyl acetate = 2 / 1) was monitored. After the raw materials were completely reacted, the reaction solution was cooled to room temperature, and 50 mL of dichloromethane was added to the reaction solution to dilute it. 100 mL of water was then added, shaken, and the layers were separated and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The mixture was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 56%.

[0066] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 84% sulfuric acid (3.98 g, 34.16 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 40°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 63%.

[0067] Example 7 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), potassium carbonate (1.38 g, 0.01 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 70°C for 12 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 52%.

[0068] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.51 g, 4.3 mmol), FeCl3 (1.62 g, 10 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 20°C for 11 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the starting materials were completely reacted to obtain a reaction solution. The reaction solution was filtered and extracted with dichloromethane (40 mL). The operation was repeated once. The organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by column chromatography with gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 48%.

[0069] S3, add N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), tetrakistriphenylphosphine palladium (1.09 g, 0.95 mmol), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (0.59 g, 0.95 mmol), cesium carbonate (10.83 g, 33.32 mmol), and 20 mL of xylene into a 100 mL four-necked flask, start stirring and heating, and set an oil bath. The temperature was 130°C, and TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) was performed. The raw materials reacted completely. After the reaction solution was cooled to room temperature, 50 mL of dichloromethane was added to the reaction solution for dilution, followed by 100 mL of water. After shaking, the reaction solution was separated into layers and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain an orange-yellow solid 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile in a yield of 65%.

[0070] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 36% hydrochloric acid (3.46 g, 34.16 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 70°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 69%.

[0071] Example 8 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.27 g, 0.012 mol), sodium hydroxide (0.60 g, 0.015 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 60°C for 14 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 63%.

[0072] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.59 g, 5 mmol), AlCl3 (0.66 g, 5 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 20°C for 5 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the starting materials were completely reacted to obtain a reaction solution. 0.5 M dilute hydrochloric acid was added to the reaction solution under an ice-water bath to adjust the pH of the reaction solution to 7. The solution was extracted with dichloromethane (40 mL) and the operation was repeated once. The organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The organic phase was purified by column chromatography with a gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 51%.

[0073] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-bis(diphenylphosphino)ferrocene (0.53 g, 0.95 mmol), potassium phosphate (7.07 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, stirred, and heated. The oil bath temperature was set to 130°C. TLC (petroleum ether / ethyl acetate = 2 / 1) was monitored. After the raw materials were completely reacted, the reaction solution was cooled to room temperature, and 50 mL of dichloromethane was added to the reaction solution to dilute it. 100 mL of water was then added, shaken, and the layers were separated and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The mixture was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 62%.

[0074] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 36% hydrochloric acid (2.16 g, 27.14 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 40°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 62%.

[0075] Example 9 A method for preparing oxcarbazepine comprises the following steps: S1. Aniline (1 g, 0.01 mol), cyanogen bromide (1.13 g, 0.01 mol), sodium carbonate (1.59 g, 0.015 mol), and 20 mL of acetonitrile were added to a 100 mL four-necked flask. Stirring and heating were initiated, and the mixture was placed in an oil bath at 50°C for 14 h. TLC monitoring (petroleum ether / ethyl acetate = 10 / 1) indicated complete reaction of the starting materials. Dichloromethane (20 mL) and water (20 mL) were added to the reaction solution for extraction. The layers were separated, and the organic phase was dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and purified by column chromatography using a gradient elution method (ethyl acetate / petroleum ether) to obtain N-phenylcyanamide as a yellow solid in a yield of 52%.

[0076] S2, 2-bromophenylacetyl chloride (1 g, 4.3 mmol), N-phenylcyanamide (0.71 g, 6 mmol), FeCl3 (0.97 g, 6 mmol), and 20 mL of dichloromethane were added to a 100 mL four-necked flask and reacted at 10°C for 9 h. TLC monitoring (petroleum ether / ethyl acetate = 2 / 1) showed that the raw materials were completely reacted to obtain a reaction solution. The reaction solution was filtered and extracted with dichloromethane (40 mL). The operation was repeated once. The organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by column chromatography with gradient elution (ethyl acetate / petroleum ether) to obtain N-(2-(2-bromophenyl)acetyl)phenyl)cyanamide as a yellow solid in a yield of 44%.

[0077] S3, N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide (1.5 g, 4.76 mmol), palladium acetate (0.21 g, 0.95 mmol), 1,1'-bis(diphenylphosphino)ferrocene (0.53 g, 0.95 mmol), cesium carbonate (10.83 g, 33.32 mmol), and 20 mL of xylene were added to a 100 mL four-necked flask, stirred, and heated. The oil bath temperature was set to 110°C and monitored by TLC (petroleum ether / ethyl acetate = 2 / 1). After the raw materials were completely reacted, the reaction solution was cooled to room temperature and diluted with 50 mL of dichloromethane. 100 mL of water was then added, shaken, and the layers were separated and extracted with dichloromethane. The organic phase was washed and dried, and the solvent was removed. The mixture was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile as an orange-yellow solid in a yield of 56%.

[0078] S4. 10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonitrile (1 g, 4.27 mmol) and 36% hydrochloric acid (2.16 g, 27.14 mmol) were added to a 50 mL four-necked flask, and stirring and heating were started. The oil bath temperature was set to 40°C and monitored by TLC (petroleum ether / ethyl acetate = 3 / 1). The raw materials were reacted completely. After the reaction solution was cooled to room temperature, 50 mL of ethyl acetate was added to the reaction solution for extraction. The organic phase was washed and dried, and the solvent was removed. The product was separated by column chromatography to obtain 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide as a white solid, i.e., oxcarbazepine, with a yield of 62%.

[0079] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. A method for preparing oxcarbazepine, characterized in that: The following steps are involved: Using 2-bromophenylacetyl chloride of Formula 1 and N-phenylcyanamide of Formula 2 as raw materials, a Friedel-Crafts reaction occurs at 0-20°C under the catalysis of a Lewis acid, whereby the chlorine atom in 2-bromophenylacetyl chloride replaces the hydrogen atom ortho to cyanamide to obtain N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide of Formula 3; N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide of formula 3 is used as a raw material, a phosphine ligand is added, and a Buchwald-Hartwig reaction is carried out at 110°C to 130°C under the action of a palladium catalyst and an alkaline reagent. The amine in N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide undergoes a cross-coupling reaction with an aromatic halide to form a CN bond to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]Azoline-5-carbonitrile; 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] azepine-5-carbonitrile as raw material, water or dichloromethane as solvent, at 40 ℃ ~ 100 ℃, acidic reagent catalyzed hydrolysis reaction to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] Azaquinone-5-carboxamide, namely oxcarbazepine, has a synthetic route as follows: .

2. The preparation method according to claim 1, characterized in that The molar ratio of the 2-bromophenylacetyl chloride to N-phenylcyanamide is 1:1-1.

2.

3. The preparation method according to claim 1, characterized in that The Lewis acid is ferric chloride or aluminum chloride, and the molar ratio of the 2-bromophenylacetyl chloride to the Lewis acid is 1:1-3.

4. The preparation method according to claim 1, characterized in that The molar ratio of the N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide to the phosphine ligand is 1:0.1-0.3, and the molar ratio of the N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide, the palladium catalyst and the alkaline reagent is 1:0.1-0.3:5-8.

5. The preparation method according to claim 1, characterized in that The phosphine ligand is 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 1,1'-bis(diphenylphosphino)ferrocene or 4,5-bisdiphenylphosphino-9,9-dimethylxanthene.

6. The preparation method according to claim 1, characterized in that The alkaline reagent is cesium carbonate, sodium tert-butoxide or potassium phosphate; the palladium catalyst is palladium acetate, tris(dibenzylidene-BASE acetone)dipalladium or tetrakistriphenylphosphine palladium.

7. The preparation method according to claim 1, characterized in that The 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]The molar ratio of azepine-5-carbonitrile to the acidic reagent is 1:6~8.

8. The preparation method according to claim 1, characterized in that The acidic reagent is hydrochloric acid or sulfuric acid.

9. The synthesis method according to claim 1, characterized in that In the Friedel-Crafts reaction, dichloromethane is used as a solvent. After the reaction is completed for 6 to 7 hours, 0.5 M to 1 M hydrochloric acid is used to remove excess Lewis acid to obtain an aqueous phase. The aqueous phase is extracted with dichloromethane. After the organic phase is washed and dried, the solvent is removed to obtain N-(2-(2-(2-bromophenyl)acetyl)phenyl)cyanamide.

10. The synthesis method according to claim 1, characterized in that In the Buchwald-Hartwig reaction, toluene, xylene or N,N-dimethylformamide is used as a solvent. After the reaction is completed for 5 to 8 hours, dichloromethane is used for extraction. The organic phase is washed with deionized water and saturated brine, dried, the solvent is removed, and column chromatography is performed to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ] Nitrogen-5-carbonitrile; during the hydrolysis reaction, after the reaction is completed for 2h~3h, a reaction solution is obtained, and the reaction solution is extracted with ethyl acetate. The organic phase is washed with deionized water and saturated brine, dried, and the solvent is removed to obtain 10-oxo-10,11-dihydro-5H-dibenzo[ b , f ]Azepine-5-carboxamide.

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