KR100710548B1 - Method for preparing s-3-amino-2,3,4,5- tetrahydro-2-oxo-1H-1-benzazepin-1-acetic acid and ester compound thereof - Google Patents

Abstract

The present invention relates to a method for preparing (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester compounds thereof, wherein the organic solvent , N-alkylation of 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one with a halogenated acetic acid ester compound in the presence of a base catalyst and a phase transfer catalyst To prepare 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound; 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester 3-amino-2,3, Preparing a 4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound; And 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound to have optical activity through diastereoisomer formation with an optically active organic acid. A method for preparing optically pure (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester compounds thereof comprising the step will be.

Benzazepine, alkylation, ammonia, tetrahydro, acetic acid, phase transfer catalyst.

Description

(s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and a method for preparing an ester compound thereof (Method for preparing (s) -3 -amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-1-acetic acid and ester compound

The present invention provides a method for preparing (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester compounds thereof represented by the following general formula (1): In more detail, a lactam group using a phase transfer catalyst using 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one as a raw material (S) -3-amino-2,3 which is economical, efficient and industrially produced by conducting a direct amino group substitution reaction using ammonia and performing optical activity using optically active organic acids after mild N-alkylation of It relates to a method for producing 4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester compounds thereof.                         

In Formula 1, R is a carbon chain or ring containing a straight or branched, saturated or unsaturated carbon chain of 1 to 10 carbon atoms, a saturated or unsaturated carbon ring, or a benzene ring.

(S) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester chemicals thereof represented by Chemical Formula 1 may be used as Known as a useful material for manufacturing.

A conventional method for preparing (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester chemicals thereof is as follows.

(S) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H using 2,3,4,5-tetrahydro1H-1-benzazepin-2-one as a starting material Conventional methods for obtaining -1-benzazepine-1-acetic acid and ester chemicals thereof (US Pat. Nos. 4,410,520, 4,473,575, and 4,575,503) have been described for preparing dichlorine-substituted compounds in chlorination reactions with phosphorus pentachloride. After removing one of the two substituted chlorine atoms through hydrogenation, a single chlorine-substituted compound was prepared and an azido substitution using azido sodium was required to introduce an amino group through hydrogenation. It is economically inefficient. In addition, N-alkylation of lactams with strong bases such as sodium hydride is not easy for industrial production.

The method mentioned in US Pat. No. 4,692,522 also reacts with 3-bromide-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one after reacting with azido sodium. Therefore, it has the same problem as the above-mentioned document.

(S) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and its by cyclization with optically pure L-kynurenine The process for obtaining ester chemicals (US Pat. Nos. 4,410,520, 4,473,575, and 4,575,503) requires the use of expensive raw materials and the need to reduce and remove unnecessary carbonyl groups derived from L-kynurenine.

Alternatively, the reactions mentioned in Helvetica Chimica Acta vol. 71, pages 337-343 (1988) and U.S. Pat. No. 5,677,297 are described as 3-brominated-2,3,4,5-tetrahydro-2-oxo-1H- After reacting 1-benzazepin-2-one with potassium phthalimide potassium and hydrolyzing it to introduce an amino group, it reacts potassium phthalimide with high molecular weight to reduce atomic efficiency and hydrolysis. There is a problem that it is not economical because the step is longer because other reactions must proceed.

        Accordingly, the present invention addresses the problem of the above-described method for preparing (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester chemicals thereof. In order to solve this problem, lactam using a phase transfer catalyst using 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one as a raw material After mild N-alkylation of the group, a direct amino group substitution reaction using ammonia was carried out, and optical activity was performed using an optically active organic acid to give (s) -3-amino-2,3,4,5-tetrahydro- The present invention has been completed by preparing 2-oxo-1H-1-benzazepine-1-acetic acid and ester compounds thereof to enable economical, efficient and industrial production.

Accordingly, an object of the present invention is to provide (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H which can be commercially produced in an efficient and economical manner through mild reaction conditions and shortening of the reaction process. A method for preparing -1-benzazepine-1-acetic acid and ester chemicals thereof is provided.

(S) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid represented by the following general formula (1) of the present invention for achieving the above object and Method for preparing an ester compound thereof is a 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzase represented by the following formula (2) in the presence of an organic solvent, a base catalyst and a phase transfer catalyst 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1 represented by the following general formula (3) by reacting pin-2-one with a halogenated acetic acid ester compound represented by the following formula (5): Preparing a benzazepine-1-acetic acid ester compound; The 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by the following Chemical Formula 3 is reacted with ammonia to perform an amino group substitution reaction. Preparing a 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by 4; And forming a diastereomer of the 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by the following formula (4) with an optically active organic acid: To have optical activity through.

Formula 1

Here, R is a C1-C10 linear or branched alkyl group.

Where X is chlorine, bromine, or iodine.

Here, X is chlorine, bromine, or iodine, and R is a straight or branched alkyl group having 1 to 10 carbon atoms.

여기서, X는 염소, 브롬 또는 요오드이며, R은 탄소수 1 내지 10의 직쇄 또는 측쇄의 알킬기이다.Here, R is a C1-C10 linear or branched alkyl group.

Wherein X is chlorine, bromine or iodine, and R is a straight or branched alkyl group having 1 to 10 carbon atoms.

Hereinafter, the present invention will be described in more detail.

As described above, in the present invention, a phase transfer catalyst and a commercially available base are used from 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one. This solution solved the problem of difficult commercial production by strong base by performing N-alkylation reaction at high yield under mild conditions, and introduced azido groups by directly introducing amino groups using ammonia or by hydrogenation with potassium phthalimide. After the reaction to solve the problem that the additional step, such as a hydrolysis step to solve the problem of longer reaction step.

In other words, the present invention is a phase transfer using the 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one represented by the formula (2) as a raw material After the mild N-alkylation reaction of the lactam group using a catalyst, the amino group substitution reaction using ammonia is carried out, and the optical activity is carried out using an optically active organic acid, thereby enabling economical, efficient and industrial production (s) -3. -Amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and a method for producing an ester compound thereof.

The first reaction process is the reaction of 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one represented by Chemical Formula 2 with the halogenated acetic acid ester represented by Chemical Formula 5. N-alkylation reaction. 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one and a halogenated acetic acid ester represented by Chemical Formula 2 under a organic solvent were subjected to a phase transfer catalyst To react. The use of phase transfer catalysts has the effect of speeding up reactions and suppressing side reactions even when using cheap bases available for commercial production.

The base catalyst which can be used at this time is various alkali metal hydroxides, such as sodium hydroxide, potassium hydroxide, lithium hydroxide; Alkoxides of various alkali metals such as sodium methoxide, sodium ethoxide and sodium tert-butoxide; Alkali metal hydrides such as sodium hydride and lithium hydride; Lithium diisopropylamide, or butyllithium and the like, preferably sodium hydroxide, potassium hydroxide, or lithium hydroxide.

Phase transfer catalysts that can be used are R ¹ R ² R ³ R ⁴ NX (where R ¹ , R ² , R ³ , and R ⁴ are the same or different alkyl or aryl groups of 1 to 4 carbon atoms, X is chlorine, bromine Or iodine), and more specifically benzyltrimethylammonium chloride, benzyltriethylammonium chloride, benzyltributylammonium chloride, tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium chloride, benzyltrimethylammonium bromide, Benzyl triethylammonium bromide, benzyl tributylammonium bromide, tetramethylammonium bromide, tetraethylammonium bromide, tetrabutylammonium bromide, benzyl trimethylammonium iodide, benzyl triethylammonium iodide, benzyltributylammonium iodide, tetramethylammonium iodide, Tetraethylammonium Iodide, Tetrabutylammonium Iodide, Hydrogen Benzyl Trimethylammonium, Hydrogen Benzyl Triethylammonium Benzyl trimethylammonium sulfate, tetrahydrogen ammonium sulfate, tetraethylammonium sulfate, or tetrabutylammonium sulfate, and the like, preferably benzyltrimethylammonium chloride, benzyltriethylammonium chloride, or benzyltributylammonium chloride. to be.

The reaction solvent may be acetonitrile, tetrahydrofuran, N, N-dimethylformamide, or dimethyl sulfoxide; Alcohol solvents such as methanol and ethanol; Or one or more of aromatic solvents such as benzene, toluene, and xylene may be used, preferably acetonitrile.

The equivalent ratio of 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one represented by Formula 2 with the halogenated acetic acid ester represented by Formula 5 is 1: 1.0-3.0, Preferably it is 1: 1.0-1.1. When the equivalent ratio with the halogenated acetic acid ester is less than 1.0, the reaction conversion rate decreases, and when it exceeds 1: 3.0, it is uneconomically unnecessary to use a lot. Reaction temperature is -50-100 degreeC, Preferably it is 0-50 degreeC, Most preferably, it is 15-35 degreeC. If the reaction temperature is less than -50 ℃ not only slow the reaction rate but also economically undesirable, if the reaction temperature exceeds 100 ℃ a lot of side reactions are inefficient. The equivalent ratio of 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one represented by the formula (2) and the base catalyst is 1: 1.0 to 2.0, preferably 1: 1.0 to 1.2. If the equivalence ratio of the base catalyst is less than 1.0, the reaction is not completed. If the equivalent ratio of the base catalyst is more than 2.0, the side reaction product is increased. The equivalent ratio of 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one represented by the formula (2) and the phase transfer catalyst is 1: 0.1 to 1.0 and preferably Is 1: 0.2 to 0.5. If the equivalence ratio of the phase transfer catalyst is less than 0.1, the reaction rate is slow and inefficient.

In the next reaction step, the halogen group of the 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by Chemical Formula 3 is reacted with ammonia to form an amino group. It is reaction to introduce.

Under an organic solvent, the 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by Formula 3 is reacted with ammonia under pressurized conditions. At this time, ammonia used may be ammonia gas or ammonia water, preferably ammonia gas.

The reaction pressure is 3 to 30 atm, preferably 10 to 20 atm. If the reaction pressure is less than 3 atm, the reaction rate is significantly slower, and if it exceeds 30 atm, it is too high pressure, making commercial production difficult. Reaction temperature is 50-150 degreeC, Preferably it is 70-110 degreeC. If the reaction temperature is less than 50 ℃ the reaction rate is slow and exceeds 110 ℃ a lot of side reactions are not efficient.

The next reaction step is a diastereomer by reacting the 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by Chemical Formula 4 with an optically active organic acid. Optically pure chiral (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1- using the solubility difference in a suitable solvent after isomer formation (S) -3-amino-2,3,4,5-tetrahydro-2-oxo represented by Chemical Formula 1 by preparing an optically active organic acid salt of an acetic acid ester compound and then removing the optically active organic acid through a neutralization reaction -1H-1-benzazepine-1-acetic acid and ester compounds thereof.

Diastereomers by reacting 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by Formula 4 with an optically active organic acid in an organic solvent Optically pure chiral (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid using solubility differences in a suitable solvent after (S) -3-amino-2,3,4,5-tetrahydro-2-oxo- represented by Chemical Formula 1 by preparing an optically active organic acid salt of an ester compound and then removing the optically active organic acid through a neutralization reaction. 1H-1-benzazepine-1-acetic acid and ester compounds thereof are prepared.

The optically active organic acid used may be L- tartaric acid, diaryl tartaric acid, malic acid, camphoric acid, camphorsulfonic acid, or mandelic acid, and the like, and preferably L-tartaric acid. The reaction solvent may be methanol, ethanol, propanol, isopropanol, butanol, tert-butanol and the like, preferably ethanol or isopropanol.                     

Bases used for removing the optically active organic acid salt include primary amines such as ammonia water, methylamine, ethylamine, propylamine, and butylamine; Secondary amines such as dimethylamine, diethylamine, and diisopropylamine; Tertiary amines such as trimethylamine, triethylamine, and diethylisopropylamine; Cyclic amines such as pyridine; Or inorganic salts such as sodium carbonate, sodium bicarbonate, sodium hydroxide, and potassium hydroxide, and the like, preferably ammonia water and sodium hydroxide.

(S) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid represented by Formula 1 after removing the optically active organic acid salt and Organic solvents used for extracting the ester compounds thereof include halogen solvents such as dichloromethane, chloroform, carbon tetrachloride, and dichloroethane; Acetic acid solvents such as methyl acetic acid, ethyl acetate, and butyl acetic acid; Aromatic solvents such as benzene, toluene, and xylene; Or various solvents which are not mixed with water such as ether solvents such as ethyl ether and propyl ether can be used.

Meanwhile, the 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by Chemical Formula 4 is reacted with an optically active organic acid to form diastereomers. In this case, only the diastereomers derived from S-form of 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by Formula 4 above The diastereomers, which are precipitated as crystals by the difference in solubility and derived from the opposite optical isomer, Rform, remain in solution and are thus optically pure (s) -3-amino-2,3,4,5-tetrahydro-2. Optically active organic acid salts of oxo-1H-1-benzazepine-1-acetic acid ester compounds can be selectively obtained, but the theoretical yield will not exceed 50%. However, the diastereomers derived from 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound of R-form dissolved in the reaction solvent are aldehyde compounds. And an imine compound to form an racemic compound, and then racemize it to form part of the R-form as 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1- Converted to diastereomers of acetic acid ester compounds. Because of the difference in solubility, the material precipitates back into crystals, which theoretically allows 100% conversion of the R-form to the S-form, thus increasing the overall yield.

(s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid through tertiary butyl ester through reaction with hydrogen chloride gas (s)- 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid was obtained.

In addition, various (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compounds may be hydrolyzed to (s) -3- Amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid, of which (s) -3-amino-2,3,4,5 In the case of tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid benzyl ester, it is also possible to (s) -3-amino-2,3,4,5-tetrahydro-2 by hydrogenation instead of hydrolysis. Oxo-1H-1-benzazepine-1-acetic acid was possible.

Hereinafter, the present invention will be described in more detail with reference to the following Examples, but the scope of the present invention is not limited to the following Examples.

       Example 1

Acetonitrile (30 mL), 3-brominated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one (10 g) and tert-butyl chloroacetate in a 100 mL reactor Ester (6.6 g) was added and stirred. Benzyltriethylammonium chloride (0.38g) was added as a phase transfer catalyst, and sodium hydroxide (1.8g) was slowly added thereto, and stirred at 25 ° C for 1 hour. The reaction solution was slowly poured into water (90 g), and then the resulting solid was filtered to 3-bromide-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid tert-butyl Ester (14.1 g) was obtained.

      Example 2

Acetonitrile (30 mL) and 3-brominated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid tert-butyl ester (2 g) were added to a 100 mL high-pressure reactor. After pressurizing the ammonia gas to 10 atm, the reaction temperature was raised to 100 ° C. and stirred for 10 hours. The solvent was distilled off under reduced pressure, and then chromatographed to separate 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid tert-butyl ester (1.2 g). Got it.

      Example 3

Isopropyl alcohol (25.0 g) and 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid tert-butyl ester (6.0 g) were added to a 100 ml reactor. It heated up at 70 degreeC after putting. L-tartaric acid (3.2g) was added and stirred for 1 hour, then salicylic aldehyde (0.13g) was added and refluxed for 18 hours. The resulting solid was filtered and washed with isopropyl alcohol to obtain optically pure (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid tertiary Butyl ester tartaric acid salt was obtained. The resulting (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid tert-butyl ester tartaric acid salt (10 mL) and 28% aqueous ammonia (11 mL), followed by extraction with dichloromethane and removal of the aqueous layer. The extracted organic layer was dried with anhydrous magnesium sulfate, and then distilled under reduced pressure to obtain optically pure (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1. - to obtain ethyl tert-butyl ester (4.3g) (mp 111 ~ 113 ℃, [α] 25 D = -272.6 ℃ (C = 1.0, ethanol)).

      Example 4

In a 100 ml reactor, (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid tert-butyl ester (4.0 g) and dichloromethane (30 Ml) and hydrogen chloride gas was blown for 2 hours while maintaining the room temperature. Dichloromethane was distilled under reduced pressure to obtain (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid (4.1 g) hydrochloride. 30 ml of ethyl acetate and 30 ml of water were added to (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid (4.1 g) hydrochloride. The pH of the aqueous solution was adjusted to 7 using sodium hydroxide, and extracted (30 ml of ethyl acetate x 2). The ethyl acetate solution was evaporated under reduced pressure using anhydrous magnesium sulfate, followed by (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1. Acetic acid was obtained (mp 275 to 276 ° C).

Example 5

5% palladium catalyst (0.03 g) supported on methanol (70 mL) and activated carbon in a 100 mL reactor and (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1 Benzazepine-1-acetic acid benzyl ester (3.0 g) was added thereto, and the mixture was stirred for 3 hours while maintaining 25 ° C under hydrogen at 3 atmospheres. The catalyst was filtered off and the methanol was distilled under reduced pressure to afford (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid (1.6 g). (Mp 274.9-275.4 degreeC, [(alpha)] 20D = -295.5 degreeC (C = 0.71, 1N HCl).

As described above, the method of preparing (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid and ester compounds thereof according to the present invention Gentle N-alkylation of lactam group using phase transfer catalyst using 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one as a starting material After a direct amino-substituted reaction using ammonia, it is a very economical, efficient and industrial production method that has optical activity using optically active organic acid.

Claims (8)

In the presence of an organic solvent, a base catalyst and a phase transfer catalyst, 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one represented by the following formula (2) is represented by N-alkylation reaction with a halogenated acetic acid ester compound represented by 5 to 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid represented by the following general formula (3): Step of preparing an ester compound: wherein the organic solvent is selected from the group consisting of acetonitrile, tetrahydrofuran, N, N-dimethylformamide, dimethyl sulfoxide, methanol, ethanol, benzene, toluene, or xylene , Wherein the base catalyst is selected from the group consisting of alkali metal hydroxides, alkali metal alkoxides or alkali metal hydrides, and the phase transfer catalyst is R ¹ R ² R ³ R ⁴ NX, wherein R ¹ , R ² , R ³ , And R ⁴ are the same as or different from each other An alkyl or aryl group having 1 to 4 carbon atoms and X is chlorine or bromine or iodine; Substituting the amino group by reacting the 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by Formula 3 with ammonia in the presence of the organic solvent Preparing a 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by the following Chemical Formula 4 through the reaction; And 3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid ester compound represented by the following formula (4) through diastereoisomer formation with an optically active organic acid Optically pure (s) -3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benne represented by the following Chemical Formula 1, comprising the step of having optical activity: Method for preparing jazepin-1-acetic acid and ester compound thereof. Formula 1

Here, R is a C1-C10 linear or branched alkyl group. Formula 2

Where X is chlorine, bromine, or iodine. Formula 3

Here, X is chlorine, bromine, or iodine, and R is a straight or branched alkyl group having 1 to 10 carbon atoms. Formula 4

Here, R is a C1-C10 linear or branched alkyl group. Formula 5

Wherein X is chlorine, bromine or iodine, and R is a straight or branched alkyl group having 1 to 10 carbon atoms. delete The method of claim 1 wherein the alkali metal hydroxide is selected from sodium hydroxide, potassium hydroxide, or lithium hydroxide. delete delete The equivalence ratio of the halogenated acetic acid ester compound to 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one is 1: 1.0 to 3.0. The equivalent ratio of the base catalyst to the 3-halogenated-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-2-one is 1: 1.0 to 2.0. , The equivalent ratio of the phase transfer catalyst is 1: 0.1 to 1.0 and the reaction temperature is -50 to 100 ℃. The method of claim 1, wherein the reaction pressure of the amino group substitution reaction is 3 to 30 atm and the reaction temperature is 50 to 150 ℃.