JPH08231477A - Production of optically active beta-aminoesters - Google Patents

Abstract

PURPOSE: To obtain the subject compound useful as a synthetic intermediate for pharmaceuticals and agrochemicals in high asymmetric yield, optical purity and production yield by reacting an α,β-unsaturated ester compound with an amine compound in the presence of a catalyst. CONSTITUTION: This compound of formula III (* represents an asymmetric carbon atom of S-configuration or R-configuration) is produced by reacting (A) a compound of formula I [R<1> and R<2> are each H, an alkyl or a (substituted) aryl provided that R<1> is different from R<2> ; R<3> is an alkyl or a (substituted)aryl] with (B) a compound of formula II [R<4> and R<5> are each H, a (substituted)aryl, a (substituted)aralkyl or an alkyl provided that at least one of the substituents R<1> , R<2> and R<3> and at least one of the substituents R<4> and R<5> are optically active substituents having asymmetric carbon atoms] in the presence of (C) a trisubstituted rare earth metal (e.g. scandium triflate).

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for synthesizing optically active β-aminoesters useful as synthetic intermediates for medicines and agricultural chemicals. More specifically, an optically active β-aminoester is produced by reacting a raw material α, β-unsaturated ester compound with an amine compound in the presence of a catalyst to induce a new asymmetric center. It is about how to do it.

[0002]

BACKGROUND ART β-Amino esters are known as a partial structure of natural organic compounds having physiological activity, and particularly, optically active substances derived from an asymmetric carbon atom substituted with an amino group are important. Further, the β-amino ester compound is, for example, KRI 13 which is a drug having an ACE inhibitory action.
It is also used as a synthetic precursor of 14 and as a synthetic intermediate for β-lactams having an antibacterial action (J. Am. Chem. So.
c., 114, 5427, 1992).

The methods for producing optically active β-aminoesters are roughly classified into the following four methods: (a) Elongation of carbon side chain of optically active α-aminoesters easily available from natural products To give β-aminoesters;
(b) a method of converting from an optically active aspartic acid derivative that is a natural β-amino acid;
(d) A method of reacting α, β unsaturated esters with amines is known.

However, the first method has a problem that the kinds of amino acids used as raw materials are limited, and that multisteps are required to produce optically active β-aminoesters having a desired substituent. In some cases, it may be difficult to produce the target compound. In addition, the second and third methods require multiple steps for conversion of a specific compound, an aspartic acid derivative or a β-aminoglutaric acid derivative, into an optically active β-aminoester having a desired substituent, It was sometimes impossible to manufacture. In addition, the fourth
Method is a method by which the production of various optically active β-aminoesters can be designed, but generally requires low reaction because of severe reaction conditions, low yield, and long reaction time. In addition, there are problems such as low optical purity of the obtained β-aminoesters.

The fourth method is, for example, a method of performing the reaction under high pressure (d'Angelo, et al., J. Am. Chem. S.
oc., 108, 8112, 1986), using silylated amine and lithium amide (Yamamoto, et al., Tetrahedro.
n, 46, 4563, 1988) and a method using lithium amide (Davies, et al., Synlett, 1944, 117). However, these methods
Since high-pressure reaction equipment and special equipment such as handling lithium amide are required, it was difficult as an industrial production method. In addition, optically active β using ytterbium
-Synthetic methods of aminoesters have also been proposed (Chemi
stry Letters, 1994, 827), except that the substrate used in the reaction has asymmetry at the γ-position of the ester, the asymmetric yield is low and not practical.

[0006]

The object of the present invention is to efficiently use β
-To provide a method for producing an amino ester compound. More specifically, the present invention relates to a method of reacting an α, β unsaturated ester with an amine (the above-mentioned fourth method).
The present invention aims to provide a method for efficiently producing a β-amino ester compound. In particular, an object of the present invention is to provide a method for producing an optically active β-aminoester compound by inducing an asymmetric center in a carbon atom which an amino group substitutes in the above method. From another point of view, the object of the present invention is to obtain optically active β with high asymmetric yield.
-To provide a method for producing an amino ester compound and a method for producing an optically active β-amino ester compound having high optical purity.

[0007]

Means for Solving the Problems As a result of diligent efforts to solve the above problems, the present inventors have produced amines of β-amino ester compounds by reacting amines with α, β unsaturated esters. On the other hand, when the reaction is carried out in the presence of a tri-substituted rare earth metal, the reaction can be carried out extremely efficiently, and in addition, an optically active β-aminoester compound having high optical purity can be produced. I found it. The present invention has been completed based on the above findings.

That is, the present invention provides the following formula (1):

[Chemical 7] (In the formula, R ¹ and R ² each independently represent a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group,
R ¹ and R ² are not the same, and R ³ represents an alkyl group or a substituted or unsubstituted aryl group) and an α, β-unsaturated carboxylic acid ester compound represented by the following formula
(2):

Embedded image (In the formula, R ⁴ and R ⁵ are each independently a hydrogen atom, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, or an alkyl group) (provided that R ¹ and R ^At least one substituent selected from the group consisting of ² , and R ³ and / or at least one substituent selected from the group consisting of R ⁴ and R ⁵ has 1 or 2 or more asymmetric carbon atoms An optically active substituent) with a tri-substituted rare earth metal in the presence of the following formula (3):

[Chemical 9] (Wherein R ¹ , R ² , R ³ , R ⁴ , and R ⁵ are as defined above, and * represents an asymmetric carbon atom in S-configuration or R-configuration) The present invention provides a method for producing a β-amino ester compound, more preferably an optically isomerically pure β-amino ester compound.

According to a preferred embodiment of the present invention, the above method using an achiral compound as the compound of formula (1) and an optically active amine compound as the compound of formula (2);
Method using an optically active compound as the compound of formula (2) and an achiral amine compound as the compound of formula (2);
There is provided the above method, wherein an optically active compound is used as the compound of (1) and an optically active amine compound is used as the compound of formula (2).

According to still another preferred embodiment of the above invention, the compound of formula (1) has the following formula (4E):

[Chemical 10] Or the following formula (4Z):

[Chemical 11] [In the above formulas, R ¹ and R ³ are as described above, and R ⁶
Represents a substituted or unsubstituted aryl group or alkyl group, R ⁷ represents a substituted silyl group or a methyl group substituted with a phenyl group or an alkoxyl group), and the compound of formula (3) is Expression (5):

[Chemical 12] (Wherein R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are the same as above, and * represents an asymmetric carbon atom in S-configuration or R-configuration) The above-mentioned method, wherein the trisubstituted rare earth metal is selected from the group consisting of scandium triflate, yttrium triflate, lanthanum triflate, samarium triflate, and europium triflate; and a catalytic amount of the trisubstituted rare earth metal. Provided is the above method for use.

The method of the present invention is characterized by reacting the compound of formula (1) with the compound of formula (2) in the presence of trisubstituted rare earth metals. In the compounds of formulas (1) and (3), R ¹ and R ² each independently represent a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group.
In the present specification, the alkyl group may be a linear, branched, or cyclic alkyl group, and examples thereof include a lower alkyl group having 1 to 6 carbon atoms, and a cyclic alkyl group which is a crosslinked group or an optically active group. May be
Further, it may have a substituent. Preferably 1 carbon
Can be used, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, An n-hexyl group and an isohexyl group are preferred alkyl groups. As the cyclic alkyl group, a menthyl group, a bornyl group, an 8-phenylmenthyl group, an 8-naphthylmenthyl group and the like are preferable.

As the substituted or unsubstituted aryl group, for example, a substituted or unsubstituted phenyl group or a naphthyl group, preferably an unsubstituted phenyl group can be used. Examples of the substituted aryl group include a halogen-substituted aryl group and an alkoxy-substituted aryl group such as a chlorophenyl group, a fluorophenyl group and a methoxyphenyl group.

In the compounds of formulas (1) and (3), R ³ represents an alkyl group or a substituted or unsubstituted aryl group, and as the alkyl group or aryl group, for example, those exemplified above can be used. it can. The reaction can also be performed using a compound in which R ³ is a hydrogen atom (α, β-unsaturated carboxylic acid). In the compounds of formula (2) and formula (3), R ⁴ and R ⁵ each independently represent a hydrogen atom, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, or an alkyl group, an aryl group, As the alkyl group, those exemplified above can be used, and as the aralkyl group, for example, a benzyl group, a phenethyl group, a naphthylethyl group or the like can be used, and these may be substituted or unsubstituted. For example, as the substituted benzyl group, a methoxybenzyl group,
A chlorobenzyl group or the like can be used.

The method of the present invention is characterized in that the amine compound (2) is stereoselectively added to the β-carbon atom of the compound (1) to induce asymmetry on this carbon atom.
In the compound of the above formula (1) and the compound of the formula (3) produced by the method of the present invention, R ¹ and R ² do not simultaneously represent the same substituent. That is, in the compound (3) obtained by the method of the present invention, R ¹ and R ² marked with * are
The carbon atom that is replaced by is always an asymmetric carbon and is either in the S-configuration or the R-configuration. Compound (1) and / or compound (2) used in the method of the present invention is an optically active substance having at least one asymmetric carbon atom, preferably an optically isomerically pure compound. More specifically, in the compounds (1) and (2), at least one substituent selected from the group consisting of R ¹ , R ² , and R ³ and / or a group consisting of R ⁴ and R ⁵ At least one substituent selected is an optically active substituent having one or more asymmetric carbons.

Therefore, in the compound (3), at least one asymmetric carbon is present in addition to the carbon atom marked with *, and when complete induction of asymmetry is not achieved, S-configuration or A compound (3), which is a mixture of diastereomers with an excess of the compound (3) having any of the R-configuration carbon atoms, is produced, and such diastereomeric excess (d, e,) The compound (3) in the form of is also included in the scope of the present invention. Needless to say, the method of the present invention proceeds efficiently even if R ¹ and R ² have the same substituent.

For example, as the compound of formula (1), ethyl crotonate, methyl cinnamate, (-)-menthyl crotonate, (+)-menthyl crotonate, (-)-bornyl cinnamate, (+)- Bornyl cinnamate, (-)-8-phenylmenthyl crotonate, (+)-8-phenylmenthyl crotonate, (E) -methyl- (4S) -t-butyldimethylsilyloxy
-2-Pentenoate, (E) -methyl- (4R) -t-butyldimethylsilyloxy-2-pentenoate, (Z) -methyl- (4S) -t-
Butyldimethylsilyloxy-2-pentenoate, or
(Z) -methyl- (4R) -t-butyldimethylsilyloxy-2-pentenoate and the like can be used. Further, as the amine compound of the formula (2), in addition to ammonia, methylamine,
Ethylamine, benzylamine, phenethylamine, etc.
Naphthylethylamine, (-)-phenethylamine, (-)-1-
(1-Naphthyl) ethylamine and the like, and amino acids such as D- or L-alanine and the like can be used.

According to a preferred embodiment of the present invention, an achiral ester such as ethyl crotonate or ethyl cinnamate is used as the compound of formula (1), and (-)-
Method using optically active amine such as phenethylamine, (-)-1- (1-naphthyl) ethylamine; (-)-menthyl crotonate, (-)-8-phenylmenthyl crotonate, etc. as the compound of formula (1) A method of using an optically active ester and an achiral amine such as benzylamine as an amine; and a method of using an optically active ester as the compound of formula (1) and an optically active amine as the amines are provided.

According to another preferred embodiment of the method of the present invention, there is provided a method of using the compound represented by the above formula (4E) or (4Z) as the compound of formula (1). In the above formulas, R ¹ and R ³ are as described above, R ⁶ represents a substituted or unsubstituted aryl group or alkyl group, R ⁷ represents a substituted silyl group, or a phenyl group or an alkoxyl group,
For example, a methyl group substituted with an alkoxyl group having 1 to 6 carbon atoms is shown. As the alkyl group represented by R ⁶ , those exemplified above can be used. As the aryl group, a phenyl group, a naphthyl group or the like can be used,
A chlorophenyl group, a methoxyphenyl group, etc. can be used as a substituted aryl group. As R ⁷ , use a substituted silyl group such as a trimethylsilyl group, an isopropyldimethylsilyl group, a tribenzylsilyl group, t-butyldimethylsilyl, or a t-butyldiphenylsilyl group, or a substituted methyl group such as methoxymethyl, benzyl or trityl. You can

In the above preferred embodiment, as the compound of formula (1), for example, (E) -methyl- (4S) -t-butyldimethylsilyloxy-2-pentenoate, (Z) -methyl- (4S)- Using t-butyldimethylsilyloxy-2-pentenoate, (E)-(-)-menthyl- (4S) -t-butyldimethylsilyloxy-2-pentenoate, etc., benzylamine, etc. as the amine compound of formula (2) Or an optically active amine such as (-)-phenethylamine or (-)-1- (1-naphthyl) ethylamine.

The tri-substituted rare earth metal used in the method of the present invention is not particularly limited, but scandium triflate, yttrium triflate, lanthanum triflate, samarium triflate, europium triflate, etc. can be preferably used. When carrying out the method of the present invention, the order of adding the reaction reagents to the reaction system is not particularly limited, and amines, esters, and trisubstituted rare earth metals can be added in any order. As an example, the method of the present invention can be carried out by adding the compound of the formula (1) and the amine compound (2) to the above trisubstituted rare earth metal without solvent. When a solvent is used, the type of the solvent is not particularly limited as long as it is inert in the reaction, but examples thereof include ethers such as tetrahydrofuran and ethyl ether; halogenated hydrocarbons such as dichloromethane and chloroform; N, N-dimethylformamide. And amides such as dimethylacetamide; aliphatic hydrocarbons such as hexane;
Aromatic hydrocarbons such as benzene and toluene; alcohols such as methanol and ethanol; or acetonitrile and dimethyl sulfoxide can be used.

The ratio of the compound of the formula (1) to the amine compound of the formula (2) is not particularly limited, but for example, the compound 1 of the formula (1)
It is preferable to use about 1.5 equivalents of the amine compound of the formula (2) with respect to equivalents. Considering the purification of the product, it is not preferable to use one in a large excess. The tri-substituted rare earth metal may be added in a catalytic amount, but may be added in an amount of several times the catalytic amount, preferably 3 times or less. The amount of such a catalyst can be appropriately determined by those skilled in the art depending on the kind of the raw material compound used and the reaction conditions. The reaction is usually performed in the range of -78 ° C to 90 ° C, and usually completed within a few minutes to a few days.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples. In the following examples, diastereomers having a high polarity are defined as P isomers and those having a low polarity are defined as L isomers.

[0023]

【Example】

[Example 1] Optically active isopropyl 3-N-[(1S) -1-naphthylethyl] a
Minobutyrate under a nitrogen stream, scandium triflate (49.2 mg, 0.1 mmo
l) and isopropyl crotonate (128.2 mg, 1.0 mmol)
Was stirred at room temperature for 30 minutes. Then, (1S) -N-1-naphthylethylamine (240.1 μl, 1.5 mmol) was added, and the mixture was stirred at the same temperature for 20 hours. Methylene chloride was added to this reaction mixture, which was washed with a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over magnesium sulfate. After evaporating the solvent, the obtained crude product was subjected to flash silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to give the title compound as a diastereomer, and the L form (42.6 mg) and the P form were obtained.
(116.2 mg) was obtained (53%, 46% de).

L-form; ¹ H-NMR (CDCl ₃ ) δ: 1.11 (3H, d, J = 6.6 Hz), 1.23 (6
H, d, J = 6.1 Hz), 1.47 (3H, d, J = 6.1 Hz), 1.64 (1
H, bs), 2.40 (2H, d, J = 6.1 Hz), 3.10 (2H, m), 4.75
(1H, q, J = 6.6 Hz), 5.00 (1H, m, J = 6.1 Hz), 7.43
-8.24 (7H, m). P-form; ¹ H-NMR (CDCl ₃ ) δ: 1.07 (3H, d, J = 6.5 Hz), 1.19 (6
H, d, J = 6.1 Hz), 1.46 (3H, d, J = 6.1 Hz), 1.84 (1
H, bs), 2.30 (1H, dd, J = 5.1, 15.2 Hz), 2.41 (1H, d
d, J = 7.6, 15.2 Hz), 3.03 (2H, m), 4.81 (1H, q, J =
6.5 Hz), 5.01 (1H, m, J = 6.1 Hz), 7.43-8.20 (7H,
m).

[Example 2] Optically active (-)-8-phenylmenthyl 3-N-benzylaminobu
Chireto under a stream of nitrogen, scandium triflate (49.2mg, 0.1mm
ol) and (-)-8-phenylmenthyl crotonate (300.5
mg, 1.0 mmol) was stirred at room temperature for 30 minutes. Benzylamine (160.7mg, 1.5mmol) was then added and at that temperature
It was stirred for 72 hours. Methylene chloride was added to this reaction mixture, which was washed with a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over magnesium sulfate. After distilling off the solvent, the obtained crude product was subjected to flash silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to recover 113.0 mg of (-)-8-phenylmenthyl crotonate. Was used as a diastereomer to obtain L-form (156.1 mg) and P-form (49.3 mg) (81%, 52% de).

L-form; ¹ H-NMR (CDCl ₃ ) δ: 0.85-2.04 (23H, m), 2.87 (1H,
m), 3.70 (2H, dd, J = 12.8, 29.3 Hz), 4.79 (1H, dt, J
= 4.4, 10.7 Hz), 7.10-7.32 (10H, m). P-body; ¹ H-NMR (CDCl ₃ ) δ: 0.84-2.05 (23H, m), 2.90 (1H,
m), 3.69 (2H, dd, J = 13.3, 23.1 Hz), 4.81 (1H, dt, J
= 4.4, 10.7 Hz), 7.10-7.32 (10H, m).

[Example 3] Optically active (-)-8-phenylmenthyl 3-N-[(S) -α-methyl ester
Njiru] aminobutyrate nitrogen stream, scandium triflate (49.2mg, 0.1mmo
l) and (-)-8-phenylmenthyl crotonate (300.5m
g, 1.0 mmol) was stirred at room temperature for 30 minutes. Then, (S) -α-
Methylbenzylamine (181.8 mg, 1.5 mmol) was added, and the mixture was stirred at the same temperature for 72 hours. Methylene chloride was added to this reaction mixture, which was washed with a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over magnesium sulfate. After evaporating the solvent, the obtained crude product was subjected to flash silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to recover 177.2 mg of (-)-8-phenylmenthyl crotonate. As a mixture of diastereomers, 11
5.7 mg was obtained (67%). The diastereoselectivity of this compound was determined by measuring 1H-NMR (73% de).

¹ H-NMR (CDCl ₃ ) δ: 0.81-2.02 (26H, m),
2.63 (1H, m; major), 2.78 (1H, m; minor), 3.77 (1H,
q, J = 6.6Hz; minor), 3.84 (1H, q, J = 6.6Hz), 4.76
(1H, m), 7.09-7.33 (10H, m).

[Example 4] Optically active (-)-8-phenylmenthyl 3-N-[(R) -α-methyl ester
Njiru] aminobutyrate nitrogen stream, scandium triflate (49.2mg, 0.1mmo
l) and (-)-8-phenylmenthyl crotonate (300.5m
g, 1.0 mmol) was stirred at room temperature for 30 minutes. Then, (R) -α-
Methylbenzylamine (181.8 mg, 1.5 mmol) was added, and the mixture was stirred at the same temperature for 72 hours. Methylene chloride was added to this reaction mixture, which was washed with a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over magnesium sulfate. After evaporating the solvent, the obtained crude product was subjected to flash silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to give the title compound as a diastereomer and the L-form (266.1
mg) and P-form (82.2 mg) were obtained (83%, 53% de).

L-form; ¹ H-NMR (CDCl ₃ ) δ: 0.86-2.06 (26H, m), 2.73 (1H, d
t, J = 6.3, 12.3 Hz), 3.72 (2H, q, J = 6.6 Hz), 4.81
(1H, dt, J = 4.3, 10.6 Hz), 7.11-7.33 (10H, m). P-body; ¹ H-NMR (CDCl ₃ ) δ: 0.84-2.01 (26H, m), 2.67 (1H,
m), 3.82 (2H, q, J = 6.6 Hz), 4.77 (1H, dt, J = 4.3, 1
0.9 Hz), 7.10-7.36 (10H, m).

Example 5 Optically Active Methyl- (4S) -4-t-butyldimethylsilyloxy-N
- benzylamino pentenoyl rate under a nitrogen gas stream, scandium triflate (49.2mg, 0.1mmo
l) and (E) -methyl- (4S) -t-butyldimethylsilyloxy
-2-Pentenoate (244.4 mg, 1.0 mmol) was stirred at room temperature for 30 minutes. Then benzylamine (160.7mg, 1.5mmol)
Was added and the mixture was stirred at the same temperature for 72 hours. Methylene chloride was added to this reaction mixture, which was washed with a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over magnesium sulfate. After evaporation of the solvent, the obtained crude product was subjected to flash silica gel column chromatography (ethyl acetate: n-hexane =
1: 2) to give 210.9 mg (60%) of the title compound as a diastereomeric mixture. The diastereoselectivity of this compound was determined by measuring ¹ H-NMR (1
4% de).

¹ H-NMR (CDCl ₃ ) δ; 0.02, 0.04 (6H, each
s; major), 0.05, 0.06 (6H, each s; minor), 0.87 (9H,
s), 1.14, 1.16 (3H, d, J = 6.4 Hz; minor), 1.15, 1.1
7 (3H, d, J = 5.9 Hz; major), 1.70 (1H, brs), 2.38-2.
61 (2H, m), 2.93-3.05 (1H, m), 3.67 (3H, s), 3.77-
3.87 (2H, m), 3.89-3.96 (1H, m; major), 3.97-4.05
(1H, m; minor), 7.22-7.33 (5H, m).

Example 6 Optically Active Methyl- (4S) -4-t-butyldimethylsilyloxy-N
- benzylamino pentenoyl rate under a nitrogen gas stream, scandium triflate (49.2mg, 0.1mmo
l) and (Z) -methyl- (4S) -t-butyldimethylsilyloxy
-2-Pentenoate (244.4 mg, 1.0 mmol) was stirred at room temperature for 30 minutes. Then benzylamine (160.7mg, 1.5mmol)
Was added and the mixture was stirred at the same temperature for 72 hours. Methylene chloride was added to this reaction mixture, which was washed with a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over magnesium sulfate. After evaporation of the solvent, the obtained crude product was subjected to flash silica gel column chromatography (ethyl acetate: n-hexane =
1: 2) to give 168.8 mg (48%) of the title compound as a diastereomeric mixture. The diastereoselectivity of this compound was determined by measuring ¹ H-NMR (4
9% de).

¹ H-NMR (CDCl ₃ ) δ; 0.02, 0.04 (6H, each
s; major), 0.05, 0.06 (6H, each s; minor), 0.87 (9H,
s), 1.14, 1.16 (3H, d, J = 6.4Hz; minor), 1.15, 1.17
(3H, d, J = 5.9Hz; major), 1.70 (1H, brs), 2.38-2.
61 (2H, m), 2.93-3.05 (1H, m), 3.67 (3H, s), 3.77-
3.87 (2H, m), 3.89-3.96 (1H, m; major), 3.97-4.05
(1H, m; minor), 7.22-7.33 (5H, m).

According to the method of the present invention, an optically active β-amino ester can be efficiently produced by using an α, β-unsaturated ester compound and an amine compound. The method of the present invention is useful because it has a high asymmetric yield and can easily produce an optically active β-amino ester from easily available raw materials.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication C07C 229/22 9450-4H C07C 229/22 229/36 9450-4H 229/36 C07F 7/10 C07F 7/10 A // B01J 31/02 103 B01J 31/02 103X C07B 61/00 300 C07B 61/00 300 C07M 7:00

Claims (8)

[Claims] 1. The following formula (1): (Wherein, R ¹ and R ² each independently represent a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, R ¹
And R ² are not the same, and R ³ represents an alkyl group or a substituted or unsubstituted aryl group) and a compound represented by the following formula (2): (In the formula, R ⁴ and R ⁵ each independently represent a hydrogen atom, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, or an alkyl group) (provided that R ¹ and R ² , And at least one substituent selected from the group consisting of R ³ and / or at least one substituent selected from the group consisting of R ⁴ and R ⁵ is an optical having one or two or more asymmetric carbon atoms. With an active substituent) in the presence of a tri-substituted rare earth metal, represented by the following formula (3): (Wherein R ¹ , R ² , R ³ , R ⁴ , and R ⁵ are as defined above, and * represents an asymmetric carbon atom in S-configuration or R-configuration). Method for producing β-amino ester compound. 2. The method according to claim 1, which produces an enantiomerically pure β-aminoester compound. 3. The method according to claim 1, wherein an achiral compound is used as the compound of formula (1) and an optically active compound is used as the compound of formula (2). 4. The method according to claim 1, wherein an optically active compound is used as the compound of formula (1) and an achiral compound is used as the compound of formula (2). 5. The method according to claim 1, wherein an optically active compound is used as the compound of formula (1) and an optically active compound is used as the compound of formula (2). 6. A compound of formula (1) is represented by the following formula (4E): Or the following formula (4Z): (In each of the above formulas, R ¹ and R ³ are as described above, and R ⁶
Represents a substituted or unsubstituted aryl group or alkyl group, R ⁷ represents a substituted silyl group or a methyl group substituted with a phenyl group or an alkoxyl group), and the compound of formula (3) is Equation (5): (Wherein R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are the same as above, and * represents an asymmetric carbon atom in S-configuration or R-configuration) The method of claim 1, wherein 7. The method according to claim 1, wherein a metal selected from the group consisting of scandium triflate, yttrium triflate, lanthanum triflate, samarium triflate, and europium triflate is used as the tri-substituted rare earth metal. . 8. The method of claim 7, wherein a catalytic amount of tri-substituted rare earth metal is used.