JPH11349539A - Production of 4-nitro ester compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a 4-nitro ester compound in a high yield and in a high selectivity under mild conditions by reacting a nitroolefin compound with a ketene silyl acetal compound in the presence of a catalyst comprising the salt of an alkylpyridine compound with a superacid. SOLUTION: This method for producing a 4-nitro ester compound of formula IV comprises reacting a nitroolefin compound of formula II (R<6> to R<8> are each H, an alkyl or the like, or form a methylene chain between R<6> and R<7> ) (for example, nitroethylene) with a ketal silyl acetal compound of formula III (R<9> and R<10> are each H, an alkyl or the like, or form a methylene group between R<9> and R<10> ; R<11> and R<12> are each an alkyl, an aryl or a halogen; R<13> is an alkyl, an alkenyl or the like) [for example, methyl(trimethylsily)dimethylketene acetal] in the presence of a 2-alkylpyridinium salt catalyst obtained by mixing a 2-alkylpyridine compound of formula I (R<1> is an alkyl; R<2> to R<5> are each H, an alkyl or the like, or form methylene chains between R<2> and R<3> , between R<3> and R<4> , and between R<5> and R<6> , respectively) (for example, 2-methylpyridine) with a superacid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing a 4-nitroester compound by reacting a nitroolefin compound with a ketene silyl acetal compound in the presence of a salt catalyst of a 2-alkylpyridine compound and a superacid. In the 4-nitroester compound obtained according to the present invention, for example, 2,2-dimethyl-4-nitro-3-
Phenyl-butanoic acid is described in J. Am. Org. Chem. , 5th
4, 1018, (1989), useful as raw materials and intermediates for pharmaceuticals and agricultural chemicals by catalytic hydrogenation using hydrogen gas in an alcohol solvent in the presence of 10% Pd / C according to the method described in (1989). 4- is a unique amino acid derivative
Derived to methyl amino-2,2-dimethyl-3-phenyl-butanoate.

[0002]

2. Description of the Related Art Conventionally, a reaction between a nitroolefin compound and a ketene silyl acetal compound has been proposed.
As a method for producing a nitroester compound, there is a method as shown below. . J. Am. Chem. Soc. , Volume 106, 21
49, (1984) discloses that a nitroolefin compound is reacted with a ketene silyl acetal compound in a system containing titanium tetrachloride alone or titanium tetrachloride and titanium tetraisopropoxide as a catalyst.
A method for preparing a -nitroester compound in a system and finally producing a 1,4-diketone compound by hydrolysis is described. However, this method has problems that the amount of the titanium compound to be used is required to be equal to that of the ketene silyl acetal compound, and that the nitroolefin compound to be used is limited to a compound in which the 1-position is a hydrogen atom. Was.

[0003] J. Org. Chem. , Volume 62,
On page 4370, (1997), a nitroolefin compound and a ketene silyl acetal compound are used as catalysts.
Methyl aluminum bis (2,6-di-tert-butyl-4-methylphenoxide) (hereinafter referred to as MAD)
A method for producing a 4-nitroester compound by reacting in a system with the addition of the compound is described. However, this method requires that the amount of catalyst used is 1 to 1.5 equivalents to the nitroolefin compound used, and the use of highly reactive alkyl aluminum at the time of catalyst preparation results in heat generation and ignition. The reaction system is complicated because, for example, it is necessary to treat the generated aluminum oxide at the end of the reaction when the reaction is completed, and furthermore, it is difficult to treat the reaction system like methyl-tert-butyldimethylsilyldimethylketene acetal. When a compound having a substituent which causes steric hindrance in a molecule is used, there is a problem that the yield is low. Therefore, any of the known manufacturing methods
-I was dissatisfied with the method for industrially producing nitroester compounds.

[0004]

SUMMARY OF THE INVENTION Accordingly, the present invention provides
As a method for producing a -nitroester compound, an industrially advantageous method, that is, a raw material compound is not limited, a small amount of a catalyst is used, a mild condition, and a complicated reaction system treatment is not required. An object of the present invention is to provide a production method for obtaining an ester compound with high yield and high selectivity.

[0005]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, a nitroolefin compound and a ketene silyl acetal compound are reacted to produce a 4-nitroester compound. In this case, by using a 2-alkylpyridinium compound composed of a 2-alkylpyridine compound and a super strong acid as a catalyst, the raw material compound is not limited, the amount of the catalyst used is small, and under a mild condition, a complicated reaction system is required. The present invention has been completed by finding a novel method capable of producing a 4-nitroester compound with high yield and high selectivity without requiring any treatment.

The present invention provides a compound represented by the general formula (1):

[0007]

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(Wherein R ¹ represents an alkyl group; R ² ,
R ³ , R ⁴ and R ⁵ are the same or different and each represent a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a halogen atom, an alkoxy group, or an aryloxy group;
Further, a methylene chain may be formed between R ² and R ^3, between R ³ and R ^{4, and} between R ⁴ and R ⁵ , and the formed methylene chain may form an aromatic ring. Formula (2) in the presence of a 2-alkylpyridium compound catalyst prepared by mixing a 2-alkylpyridine compound represented by the formula and a super strong acid.

[0009]

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(Wherein, R ⁶ , R ⁷ and R ⁸ are the same or different and each represent a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a halogen atom, an alkoxy group, an aryloxy group; , R ⁶ and R ⁷ may form a methylene chain) and a nitroolefin compound represented by the general formula (3):

[0011]

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[0012] (wherein, R ^9, R ¹⁰ are the same or different and each represents a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a halogen atom, an alkoxy group, an aryloxy group, also, R ⁹ , R ¹⁰ may form a methylene chain, provided that R ⁹ and R ¹⁰ are not hydrogen atoms at the same time, and R ¹¹ and R ¹² may be the same or different and represent an alkyl group, an aryl group, and a halogen atom. R ¹³ represents an alkyl group, an alkenyl group, an aryl group, or an aralkyl group), and a ketene silyl acetal compound represented by the following formula:
General formula (4) characterized by reacting in an organic solvent

[0013]

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Wherein R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R
¹³ has the same meaning as described above).

The method for producing the 4-nitroester compound represented by the general formula (4) of the present invention can be represented, for example, by the following reaction formula.

[0016]

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[0017]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, the alkyl group represented by R ^{1 to} R ¹³ means a linear, branched or cyclic alkyl group, for example, a methyl group, an ethyl group, a propyl group ( Butyl group (including each isomer), pentyl group (including each isomer), hexyl group (including each isomer), heptyl group (including each isomer), octyl group (including each isomer) Isomer), nonyl group (including each isomer), decyl group (including each isomer), cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group or A cyclodecyl group can be mentioned.

The alkenyl group represented by R ^{2 to} R ¹⁰ and R ¹³ means a linear, branched or cyclic alkenyl group.
For example, a vinyl group, a propenyl group (including isomers), a butenyl group (including each isomer), a pentenyl group (including each isomer), a hexenyl group (including each isomer), a heptenyl group ( Examples include an octenyl group (including each isomer), an octenyl group (including each isomer), a nonenyl group (including each isomer), and a decenyl group (including each isomer).

The aryl group represented by R ^{2 to} R ¹³ is (1)
It means “aryl group having no substituent” or (2) “aryl group having substituent”. Examples of the “aryl group having no substituent” in (1) include a phenyl group, a naphthyl group, an anthracenyl group and a thienyl group. As the substituent of the “aryl group having a substituent” in (2), for example, a hydroxyl group, an optionally substituted linear or branched C 1 -C 1
Examples thereof include 10 alkoxy groups or an optionally substituted linear or branched alkyl group having 1 to 10 carbon atoms, and the number and positions of the substituents are not limited, and are the same or different. May be substituted plurally.

The aralkyl group represented by R ^{2 to} R ¹⁰ and R ¹³ means (3) an “aralkyl group having no substituent” or (4) an “aralkyl group having a substituent”.
Examples of the “aralkyl group having no substituent” in (3) include a benzyl group and a phenethyl group. Examples of the substituent of the “aralkyl group having a substituent” in (4) include a nitro group and a linear or branched C1-C10 alkoxy group which may be substituted. The number and position of the substituents are not limited, and a plurality of the same or different substituents may be substituted.

As the halogen atom represented by R ^{2 to} R ¹² ,
For example, a fluorine atom, a chlorine atom, a bromine atom or an iodine atom can be mentioned. Examples of the alkoxy group represented by R ^{2 to} R ¹⁰ include a methoxy group, an ethoxy group, a propoxy group (including isomers), a butoxy group (including each isomer), a pentyloxy group (including each isomer), Hexyloxy group (including each isomer), heptyloxy group (including each isomer), octyloxy group (including each isomer), nonyloxy group (including each isomer), or decyloxy group (including each isomer) Linear or branched alkoxy groups having 1 to 10 carbon atoms.

The aryloxy group represented by R ^{2 to} R ¹⁰ is
(5) An "aryloxy group having no substituent" or (6) an "aryloxy group having a substituent". Examples of the “aryloxy group having no substituent” in (5) include a phenoxy group and the like. (6) “Aryloxy group having a substituent”
Examples of the substituent include a linear or branched alkyl group having 1 to 10 carbon atoms.

Examples of the 2-alkylpyridine compound represented by the general formula (1) having the above substituents R ^{1 to} R ⁵ include 2-methylpyridine, 2-ethylpyridine, and 2-n-pyridine. Propylpyridine, 2-n-butylpyridine, 2-n-pentylpyridine, 2-n-hexylpyridine, 2-n-heptylpyridine, 2-n-octylpyridine, 2-n-nonylpyridine, 2-n-decyl Pyridine, 2,3-dimethylpyridine, 2,4-dimethylpyridine, 2,5-dimethylpyridine, 2,6-lutidine, quinaldine, 2-ethylquinoline, 2,6-ter
t-butyl-4-methylpyridine and the like.

Examples of the nitroolefin compound represented by the general formula (2) having the above substituents R ^{6 to} R ⁷ include:
For example, nitroethylene, 1-nitrocyclohexene,
β-nitrostyrene, 1-nitro-2-phenyl-1-
Propene, 1-nitro-2-phenyl-1-butene, 1
-Phenyl-2-nitro-1-propene, 1-phenyl-2-nitro-1-butene, 2-nitro-3-phenyl-2-butene, trans-2-methoxy-4- (2-nitrovinyl) phenol, Trans-4-methoxy-β
-Nitrostyrene, trans-4-methyl-β-nitrostyrene, trans-β-nitro-2- (trifluoromethyl) styrene, β-nitro-2- (trifluoromethyl) styrene, trans-β-nitro-4 -(Trifluoromethoxy) styrene, trans-2- (2-nitrovinyl) thiophene, trans-β-methyl-β-nitrostyrene, trans-1-nitro-1-propene,
Trans-1-nitro-1-butene, trans-1-nitro-1-pentene, trans-1-nitro-1-hexene, trans-1-nitro-2-cyclohexyl-1-
Butene, 2-nitro-1-propene, 2-nitro-1-
Examples thereof include butene, 1-nitro-pentene, 1-nitro-1-cyclohexylethene, 2-nitro-2-butene, 2-nitro-2-pentene and 3-nitro-2-pentene.

The nitroolefin compound represented by the general formula (2) is described, for example, in Bull. Chem. Soc. Jp
n. 61, p. 4470, (1988) (a so-called nitroaldol reaction) can be produced by reacting a nitroalkane compound with a corresponding aldehyde in the presence of a base.

Examples of the ketene silyl acetal compound represented by the general formula (3) having the substituents R ^{9 to} R ¹³ include, for example, methyl (trimethylsilyl) dimethyl ketene acetal and ethyl (trimethylsilyl) dimethyl ketene acetal. Tert-butyl (trimethylsilyl) dimethyl ketene acetal, methyl (tert-
Butyldimethylsilyl) dimethylketene acetal, ethyl (tert-butyldimethylsilyl) dimethylketene acetal, tert-butyl (tert-butyldimethylsilyl) dimethylketene acetal, n-butyl (trimethylsilyl) dimethylketene acetal, n-
Butyl (tert-butyldimethylsilyl) dimethylketene acetal, methyl (trimethylsilyl) methylketene acetal, ethyl (trimethylsilyl) methylketene acetal, tert-butyl (trimethylsilyl) methylketene acetal, methyl (tert-butyldimethylsilyl) methylketene acetal, Ethyl (tert-butyldimethylsilyl) methylketene acetal, tert-butyl (tert-butyldimethylsilyl) methylketene acetal, n-butyl (trimethylsilyl) methylketene acetal, n-butyl (t
tert-butyldimethylsilyl) methylketene acetal, 1-methoxy-1-trimethylsilyloxy-2-
Methyl-1,3-butadiene, 1-methoxy-1-trimethylsilyloxymethylenecyclohexane and the like can be mentioned.

The ketene silyl acetal compound represented by the general formula (3) is described, for example, in J. Am. Org. Chem. 43, p. 1159, (1978), the ester compound can be treated with a base and reacted with a silylating agent to form an ester compound.

In the present invention, “super strong acid” refers to 100%
Acidity stronger than sulfuric acid (acidity function, H _o<-11.0 to-
11.9). For example, trifluoro
Methanesulfonic acid, perchloric acid, chlorosulfonic acid, full
Orosulfonic acid, tetrafluoroethanesulfonic acid,
Trafluoroboronic acid, hexafluorophosphoric acid, hexa
Fluorantimonic acid and the like can be mentioned, preferably
Is trifluoromethanesulfonic acid.

The 2-alkylpyridinium compound used in the present invention is prepared by arbitrarily combining the above-mentioned 2-alkylpyridine compound and a superacid. For example, a 2-alkylpyridine compound and a superacid ( For example, it can be prepared by stirring trifluoromethanesulfonic acid) with an organic solvent (for example, methylene chloride or the like) in a range of -78 ° C to room temperature. In this case, specific examples of the 2-alkylpyridinium compound include, for example, 2,6.
-Lutidine trifluoromethanesulfonate, 2-ethylpyridine trifluoromethanesulfonate or quinaldine trifluoromethanesulfonate.

The amount of the 2-alkylpyridine compound used in the preparation of the 2-alkylpyridinium compound is usually in the range of 1.0 to 5.0 mol per 1 mol of the superacid. Is preferable, especially 1.5 to
Preferably, it is used in an amount that falls within the range of 2.0 mol. When a 2-alkylpyridinium compound is used as a catalyst in the present invention, the content of the superacid in the 2-alkylpyridinium compound is specified. In this case, the amount of the superacid used is usually based on 1 mol of the nitroolefin compound. 0.01.
Preferably, it is used in an amount that falls within the range of ~ 1.0 mol,
In particular, it is preferable to use an amount in the range of 0.05 to 0.1 mol.

In the present invention, the general formula (3) used
The ketene silyl acetal compound represented by the formula (1) is preferably used in an amount usually in the range of 1.0 to 5.0 mol per mol of the nitroolefin compound, particularly preferably 1.5 to 5.0 mol.
Preferably, it is used in an amount in the range of .about.2.0 mol.

The present invention is carried out in an organic solvent. The organic solvent used is not particularly limited as long as it does not participate in the reaction. For example, a nitrile organic solvent such as acetonitrile and benzonitrile; , N-dimethylformamide, N, N-dimethylacetamide, N-
Amide-based organic solvents such as methylpyridone and dimethylimidazole; halogen-based organic solvents such as methylene chloride, chloroform and 1,2-dichloroethane; and the like, preferably nitrile-based organic solvents and halogen-based organic solvents. Particularly, acetonitrile and methylene chloride are preferred. In addition, it is preferable that the organic solvent used in preparing the 2-alkylpyridinium compound is the same as the organic solvent from the viewpoint of simplifying the reaction operation, but may be different.

The amount of the organic solvent used in the present invention is as follows:
Usually, the amount is 0.1 to 1 mmol of the nitroolefin compound.
It is preferably used in an amount in the range of 5 to 10.0 ml, particularly preferably in an amount of 1 to 2 ml.

The reaction temperature in the present invention may be a temperature up to the boiling point of the solvent usually used, but is preferably -8.
It is 0-100 degreeC, and the range of 0-40 degreeC is especially preferable. Although the reaction temperature time in the reaction of the present invention is significantly affected by the reaction temperature, the reaction is usually completed within 0.5 to 240 hours.

The 4-nitroester compound represented by the general formula (4) obtained by the present invention comprises a nitroolefin compound represented by the general formula (2) and a ketene represented by the general formula (3). Although defined by an acetal compound, such 4-nitroester compounds include, for example,
Methyl 4-nitro-2,2-dimethyl-3-phenylbutanoate tert-ethyl 4-nitro-2,2-dimethyl-3-phenylbutanoate tert-tert-butyl 4-nitro-2,2-dimethyl-3-phenylbutanoate -Butyl, 4-nitro-2,2-dimethyl-3-phenylbutanoate, 2-methyl-4-
Methyl nitro-3-phenylbutanoate, 2-methyl-4
-Ethyl nitro-3-phenylbutanoate, 2-methyl-
Tert-butyl 4-nitro-3-phenylbutanoate,
Butyl 2-methyl-4-nitro-3-phenylbutanoate, methyl 2,2-dimethyl-4-nitro-3- (4-hydroxy-3-methoxyphenyl) butanoate, 2,2
-Dimethyl-4-nitro-3- (4-methoxyphenyl) butanoate, 2,2-dimethyl-4-nitro-
Methyl 3- (4-methylphenyl) butanoate, 2,2-
Methyl dimethyl-4-nitro-3- (2-trifluoromethylphenyl) butanoate, methyl 2,2-dimethyl-4-nitro-3- (3-trifluoromethylphenyl) butanoate, 2,2-dimethyl- 4-nitro-3- (4-
Methyl trifluoromethylphenyl) butanoate, 2,2
-Methyl dimethyl-4-nitro-3- (2-thiophenyl) butanoate, 2,2-dimethyl-4-nitro-3-
Methyl (phenyl) pentanoate, methyl 2-methyl-4-nitro-3- (4-hydroxy-3-methoxyphenyl) butanoate, methyl 2-methyl-4-nitro-3- (3-methylphenyl) butanoate Methyl 2-methyl-4-nitro-3- (2-trifluoromethylphenyl) butanoate, Methyl 2-methyl-4-nitro-3- (3-trifluoromethylphenyl) butanoate, 2-Methyl-4
Methyl-nitro-3- (4-trifluoromethylphenyl) butanoate, methyl 2-methyl-4-nitro-3- (4-trifluoromethoxyphenyl) butanoate, 2-methyl-4-nitro-3- ( Methyl 2-thiophenyl) butanoate, methyl 2-methyl-4-nitro-3- (phenyl) butanoate, methyl 1- (2-nitro-1-phenylethyl) cyclohexanecarboxylate, 1-methyl-3
-Methyl nitrobutanoate, methyl 1,1-dimethyl-3-nitro-butanoate, 1,1-dimethyl-2-methyl-
Methyl 3-nitro-pentanoate, methyl 1-methyl-2-methyl-3-nitropentanoate, methyl 2-methyl-3-nitropentanoate, 1- (1-methoxycarbonyl-1-methyl) ethyl-2- Nitrocyclohexane, 1
-(1-methoxycarbonyl) ethyl-2-nitrocyclohexane or 2-methyl-2- (2'-nitrocyclohexyl).

In the present invention, a method for obtaining a 4-nitroester compound is a combination of ordinary washing and separation operations, for example, washing the reaction mixture with water, extracting with a solvent, and extracting and concentrating to obtain a crude product. For further purification, purification may be performed by column chromatography or recrystallization operation, and a purification method may be appropriately selected for each compound.

[0037]

According to the present invention, the target compound 4-nitro is reacted by reacting a nitroolefin compound with a ketene silyl acetal compound using the salt of the 2-alkylpyridine compound and a superacid as a catalyst. An ester compound can be produced under mild conditions with good yield and selectivity, and the treatment of the reaction system is simple and the desired compound can be easily obtained.

[0038]

EXAMPLES Example 1: 2,2-Dimethyl-4-nitro-
Production method of methyl 2-phenylbutanoate. To 4 ml of methylene chloride cooled to −78 ° C., 4.4 μl (0.05 mmol) of trifluoromethanesulfonic acid and 11.6 μl (0.10 mmol) of 2,6-lutidine were added and dissolved by stirring to obtain a methylene chloride solution. Was. The obtained methylene chloride solution is transformed into trans β while maintaining the same temperature.
149 mg (1.0 mmol) of nitrostyrene and 261 m of methyltrimethylsilyldimethylketene acetal
After adding g (1.5 mmol), the reaction was stirred for 96 hours while stopping the heat retention and returning to room temperature. 6 ml of water at 4 ° C. or lower was added to the obtained reaction mixture. The separated methylene chloride layer was dried by adding anhydrous magnesium sulfate, and filtered to obtain a filtrate. The obtained filtrate was concentrated under reduced pressure to distill off methylene chloride to obtain a crude product. The obtained crude product is subjected to silica gel column chromatography (Wako).
gel C-200 (trade name), eluent; n-hexane: ethyl acetate = 5: 1)
191 mg of methyl 2-dimethyl-4-nitro-2-phenylbutanoate were obtained. (Yield based on trans β-nitrostyrene = 76.1%) MS (EI: m / z); 251 (M ⁺ ) MS (CI: m / z); 252 (MH ⁺ ) NMR (CDCl ₃ , δ) ); 1.17 (3H, s), 1.20 (3
H, s), 3.69 (3H, s), 3.75 to 3.79 (1H, d
d, J = 10.8HZ, 4.4HZ), 4.76 to 4.80 (1H, d
d, J = 13.2HZ, 4.4HZ), 4.92 to 4.98 (1H, d
d, J = 13.2HZ, 10.8HZ), 7.15 to 7.33 (5H,
m)

Example 2: Preparation of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate 2.2 μl of trifluoromethanesulfonic acid (0.025
mmol) and 5.8 μl of 2,6-lutidine (0.05 m
mol) was added to 2 ml of room temperature acetonitrile and dissolved by stirring to obtain an acetonitrile solution. While maintaining the same temperature, 75 mg (0.5 mmol) of trans β-nitrostyrene and 131 mg of methyltrimethylsilyldimethylketene acetal (0.7 mg) were added to the obtained acetonitrile solution.
5 mmol) and stirred for 1 hour to react. 6 ml of water and 10 ml of methylene chloride were added to the obtained reaction mixture.
And added. The separated methylene chloride layer was dried by adding anhydrous magnesium sulfate, and filtered to obtain a filtrate. The obtained filtrate was concentrated under reduced pressure to distill off methylene chloride to obtain 124 mg of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate as a target compound. (Yield based on trans β-nitrostyrene = 99.0%)

Example 3 Preparation of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate 2.2 μl (0.025 mmol) of trifluoromethanesulfonic acid in 4 ml of methylene chloride cooled to −78 ° C.
And 5.8 μl (0.05 mmol) of 2,6-lutidine were added and dissolved by stirring to obtain a methylene chloride solution. The obtained methylene chloride solution is transformed into trans β while maintaining the same temperature.
-Nitrostyrene 75 mg (0.5 mmol) and methyltrimethylsilyldimethylketene acetal 131 mg
(0.75 mmol), and the reaction was stirred at 4 ° C. for 48 hours while stopping the heat retention and returning to room temperature. 6 ml of water at 4 ° C. or lower was added to the obtained reaction mixture. The separated methylene chloride layer was dried by adding anhydrous magnesium sulfate, and filtered to obtain a filtrate. The obtained filtrate was concentrated under reduced pressure to remove methylene chloride, thereby obtaining 139 mg of a crude product. As a result of quantifying the obtained crude product using HPLC, it was found that 122 mg of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate was contained.
(HPLC quantitative yield based on trans β-nitrostyrene = 96.8%)

Example 4: Preparation of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate 4. The 2,6-lutidine of Example 3 was replaced with 2-ethylpyridine.
The same operation as in Example 3 was carried out except that the amount was changed to 7 µl (0.005 ml), and 2,2-dimethyl-4-nitro-3
145 mg of a crude product of methyl-phenylbutanoate were obtained. As a result of quantifying the obtained crude product using HPLC, it was found that 117 mg of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate was contained.
(HPLC quantitative yield based on trans β-nitrostyrene = 92.9%)

Example 5: Preparation of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate 6.8 μl of quinaldine was added to 2,6-lutidine of Example 3.
(0.05 ml), and the same operation as in Example 3 was carried out to obtain 151 mg of a crude product of methyl 2,2-dimethyl-4-nitro-3-phenylbutanoate. As a result of quantifying the obtained crude product using HPLC, 2,2
It was found that 133 mg of methyl-dimethyl-4-nitro-3-phenylbutanoate was contained. (HPLC quantitative yield based on trans β-nitrostyrene = 90.0
%)

Example 6: 2-methyl-4-nitro-3-
Production method of methyl phenylbutanoate. To 4 ml of methylene chloride cooled to −78 ° C., 4.4 μl (0.05 mmol) of trifluoromethanesulfonic acid and 11.6 μl (0.10 mmol) of 2,6-lutidine were added and dissolved by stirring to obtain a methylene chloride solution. Was. The obtained methylene chloride solution is transformed into trans β while maintaining the same temperature.
-149 mg (1.0 mmol) of nitrostyrene and o-
After adding 240 mg (1.5 mmol) of methyl-o-trimethylsilylmethylketene acetal, the reaction was stirred for 96 hours while keeping the temperature at room temperature and returning to room temperature. 6 ml of water at 4 ° C. or lower was added to the obtained reaction mixture. The separated methylene chloride layer was dried by adding anhydrous magnesium sulfate, and filtered to obtain a filtrate. The obtained filtrate was concentrated under reduced pressure to distill off methylene chloride to obtain a crude product. The obtained crude product is subjected to silica gel column chromatography (W
The product was purified with akogel C-200 (trade name), eluent; n-hexane: ethyl acetate = 5: 1) to obtain 104 mg of the target compound, methyl 2-methyl-4-nitro-3-phenylbutanoate. (Yield based on trans β-nitrostyrene = 44.0%) MS (CI: m / z); 238 (MH ⁺ ) NMR (CDCl ₃ , δ); 1.03 to 1.05 (3H, d, J = 6.8)
3, major diastereomer), 1.22 to 1.24 (3H, d, J
= 7.32, minor diastereomer), 2.77 to 2.81 (1H,
m, major diastereomer), 2.83 to 2.91 (1H, m, mi
nor diastereomer), 3.56 (2H, s, both diastere)
omers), 3.73 (6H, s, both diastereomers), 4.
69 (1H, m, major diastereomer), 4.71 (1H, m, m
inor diastereomer), 4.74-4.80 (1H, m, major di
astereomer), 4.84 to 4.89 (1H, m, minor diastereo)
mer), 7.16 to 3.36 (10H, m, diastereomixture).

Example 7: 2-methyl-4-nitro-3-
Production method of methyl phenylbutanoate. 2.2 μl (0.025 mmol) of trifluoromethanesulfonic acid in 4 ml of methylene chloride cooled to −78 ° C.
And 5.8 μl (0.05 mmol) of 2,6-lutidine were added and dissolved by stirring to obtain a methylene chloride solution. The obtained methylene chloride solution is transformed into trans β while maintaining the same temperature.
-Nitrostyrene 75 mg (0.5 mmol) and o-methyl-o-trimethylsilylmethylketene acetal 1
After adding 20 mg (0.75 mmol), the reaction was stirred for 24 hours while stopping the temperature keeping and returning to room temperature. 6 ml of water was added to the obtained reaction mixture. The separated methylene chloride layer was dried by adding anhydrous magnesium sulfate,
Filtration gave a filtrate. The obtained filtrate was concentrated under reduced pressure to distill off methylene chloride to obtain a crude product. As a result of quantifying the obtained crude product using HPLC, it was found that 60 mg of methyl 2-methyl-4-nitro-3-phenylbutanoate was contained. (HPLC quantitative yield based on trans β-nitrostyrene = 50.9%)

Example 8 2-Methyl-4-nitro-3-
Production method of methyl phenylbutanoate. 2.2 μl (0.025 mmol) of trifluoromethanesulfonic acid was added to 2 ml of methylene chloride cooled to −78 ° C.
And 6.8 μl (0.05 mmol) of quinaldine were added and dissolved by stirring to obtain a methylene chloride solution. While maintaining the same temperature, the obtained methylene chloride solution was mixed with 149 mg (0.5 mmol) of trans β-nitrostyrene and o-methyl-o-trimethylsilylmethylketene acetal 120.
mg (0.75 mmol), and the mixture was stirred and reacted at 4 ° C. for 72 hours. 6 m of water was added to the obtained reaction mixture.
1 was added. The separated methylene chloride layer was dried by adding anhydrous magnesium sulfate, and filtered to obtain a filtrate. The obtained filtrate was concentrated under reduced pressure to distill off methylene chloride to obtain a crude product. As a result of quantifying the obtained crude product using HPLC, it was found that 147 mg of methyl 2-methyl-4-nitro-3-phenylbutanoate was contained. (HPLC quantitative yield based on trans β-nitrostyrene = 6
2.0%)

Example 9: Preparation of methyl 2-methyl-2- (2'-nitrocyclohexyl) propionate. To 2 ml of acetonitrile cooled to 0 ° C., 2.2 μl (0.025 mmol) of trifluoromethanesulfonic acid and 5.8 μl (0.05 mmol) of 2,6-lutidine were added and dissolved by stirring to obtain a methylene chloride solution. While maintaining the same temperature, the obtained methylene chloride solution was treated with 64 mg (0.5 mmol) of 1-nitrocyclohexene and 131 mg of methyltrimethylsilyldimethylketene acetal.
(0.75 mmol), and reacted by stirring at room temperature for 48 hours. 6 ml of water was added to the obtained reaction mixture. The separated methylene chloride layer was dried by adding anhydrous magnesium sulfate, and filtered to obtain a filtrate. The obtained filtrate was concentrated under reduced pressure to distill off methylene chloride.
0 mg was obtained. The obtained crude product was purified by silica gel column chromatography (Wakogel C-200 (trade name), eluent; n-hexane: ethyl acetate = 5: 1) to obtain the target compound 2-methyl-2- (2 72 mg of methyl '-nitrocyclohexyl) propionate were obtained.
(Yield based on 1-nitrocyclohexene = 63.1%) NMR (CDCl ₃ , δ); 1.14, 1.18, 1.19, 1.23 (6
H, s, both diastereomer), 1.64 to 2.86 (9H,
m, both diastereomer), 3.63, 3.65 (3H, s, bot)
h diastereomer), 3.68 (1H, m, both diastereomer)
rs).

Claims (1)

[Claims] 1. A compound of the general formula (1) (Wherein, R ¹ represents an alkyl group, and R ² , R ³ , R ⁴ , R ⁵
Are the same or different and represent a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a halogen atom, an alkoxy group, or an aryloxy group, and R ² , R ³
Or a methylene chain may be formed between R ³ and R ^{4, or} between R ⁴ and R ⁵ , and the formed methylene chain may form an aromatic ring). In the presence of a 2-alkylpyridium compound catalyst prepared by mixing a compound and a superacid, a compound of the general formula (2) (Wherein, R ^6, R ^7, R ⁸ are the same or different and each represents a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a halogen atom, an alkoxy group, an aryloxy group, also, R ⁶ , R ⁷ may form a methylene chain) and a nitroolefin compound represented by the general formula (3): (Wherein, R ⁹ and R ¹⁰ are the same or different and are each a hydrogen atom,
An alkyl group, an alkenyl group, an aryl group, an aralkyl group, a halogen atom, an alkoxy group, an aryloxy group, and a methylene chain may be formed between R ⁹ and R ¹⁰ , provided that R ⁹ , R ¹⁰ Are not simultaneously hydrogen atoms. R ¹¹ and R ¹² are the same or different and each represent an alkyl group, an aryl group, or a halogen atom, and R ¹³ represents an alkyl group, an alkenyl group, an aryl group, or an aralkyl group). Wherein the reaction is carried out in an organic solvent. (Wherein R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , and R ¹³ have the same meanings as described above).