JP3234917B2 - Method for producing 2-exomethylene penum derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for producing a 2-exomethylenepenam derivative.

[0002]

2. Description of the Related Art Conventionally, general formula (2)

[0003]

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[Wherein R ¹ represents a hydrogen atom, a halogen atom, an amino group or a protected amino group. R ² is a hydrogen atom, a halogen atom, a lower alkoxy group, a lower acyl group,
It represents a lower alkyl group, a hydroxyl group or a protected hydroxyl group having a lower alkyl group, a hydroxyl group or a protected hydroxyl group as a substituent. Alternatively, R ¹ and R ² may combine with each other to form an oxo group. R ³ represents a hydrogen atom or a carboxylic acid protecting group. As the 2-exomethylene penum derivative represented by the formula (1), only compounds in which R ¹ is an amino group and R ² is a hydrogen atom are known. Only the method described in Chem. Soc., Chem. Commun., 81 (1987) is known. However,
According to this method, the target compound can be obtained only in a low yield, and complicated reaction operations and separation operations are required in various parts of the reaction process, which is not satisfactory as a practical production method at all. .

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method which is free from the drawbacks of the above-mentioned conventional method, is safe, easy to operate, is industrially advantageous, and has a high yield and high purity.
-To provide a method capable of producing an exomethylene penum derivative.

[0006]

According to the present invention, the general formula (1)

[0007]

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Wherein R ¹ , R ² and R ³ are as defined above. Wherein the allenyl β-lactam compound represented by the general formula (2) is electrolytically reduced to obtain a 2-exomethylene penum derivative represented by the general formula (2).

In the present invention, the allenyl β-lactam compound represented by the general formula (1) used as a starting material is a novel compound not described in the literature. For example, an azetidinone derivative represented by the general formula (3) It can be produced by reacting with a base.

[0010]

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Wherein R ¹ , R ² , R ³ and X are as defined above. R ⁵ represents a lower alkyl group which may have a substituent or an aryl group which may have a substituent. The compound of the general formula (3) can be produced, for example, according to the method described in JP-A-61-165367.

Each group shown in the present specification is more specifically as follows. In the following description, unless otherwise specified, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. As the lower alkyl group, for example, methyl, ethyl,
Examples thereof include C _1-4 linear or branched alkyl groups such as n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl groups. Examples of the aryl group include a phenyl and naphthyl group.

The protected amino group represented by R ¹ includes Protective Group in Organic
Synthesis (Protective Groups in Organic Synthesi)
s, by Theodora W. Greene;
Chapter 7 (pages 218 to 287), phenoxyacetamide, p-methylphenoxyacetamide, p-methoxyphenoxyacetamide, p-chlorophenoxyacetamide, p-bromophenoxyacetamide, phenyl Acetamide, p-methylphenylacetamide, p-methoxyphenylacetamide, p-chlorophenylacetamide, p-bromophenylacetamide, phenylmonochloroacetamide, phenyldichloroacetamide, phenylhydroxyacetamide, phenylacetamide, phenylacetoxyacetamide, α-oxophenylacetamide , Benzamide, p-methylbenzamide, p-methoxybenzamide, p-chlorobenzamide, p-bromobenzamide, Protected phenylglycyl amides of E sulfonyl glycyl amide or amino group, p- one or both of the hydroxyphenyl glycyl amide or an amino group and a hydroxyl group may be exemplified a protected p- hydroxyphenyl glycyl amide. Examples of the protecting group for the amino group of phenylglycylamide and p-hydroxyphenylglycylamide include various groups described in Chapter 7 (pages 218 to 287) of the above document. Examples of the protecting group for the hydroxyl group of p-hydroxyphenylglycylamido include various groups described in Chapter 2 (pages 10 to 72) of the above document.

The lower alkoxy group represented by R ² includes, for example, a C _1-4 linear group such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy groups. And branched alkoxy groups.

The lower acyl group represented by R ² includes, for example, C _1-4 linear or branched acyl groups such as formyl, acetyl, propionyl, butyryl, isobutyryl and the like.

The protected hydroxyl group of a lower alkyl group having a hydroxyl group or a protected hydroxyl group represented by R ² as a substituent, and the protected hydroxyl group of a protected hydroxyl group represented by R ² are described in Chapter 2 of the above document. (Pages 10 to 72). The above-mentioned substituted lower alkyl group represented by R ² may be the same or different type of a substituent selected from a hydroxyl group or the protected hydroxyl group shown above, and may be substituted on the same or different carbon by one or more. Good.

Examples of the protecting group for the carboxylic acid represented by R ³ include various groups described in Chapter 5 (pages 152 to 192) of the above literature, as well as a benzyl group, a p-methoxybenzyl group and a p-methoxybenzyl group. -Nitrobenzyl group, diphenylmethyl group,
Examples thereof include a trichloroethyl group and a tert-butyl group.

Examples of the nitrogen-containing aromatic heterocyclic group of the nitrogen-containing aromatic heterocyclic group which may have a substituent represented by R ⁴ include, for example, thiazol-2-yl and thiadiazole-2
-Yl, benzothiazol-2-yl, oxazole-
2-yl, benzoxazol-2-yl, imidazol-2-yl, benzimidazol-2-yl, pyrimidinyl, pyridyl group and the like. Examples of the type of substituent that may be substituted on the aryl group or the nitrogen-containing aromatic heterocyclic group represented by R ⁴ include a halogen atom, a hydroxyl group, a nitro group, a cyano group, an aryl group, a lower alkyl group, an amino group, mono-lower alkylamino group, a di-lower alkylamino group, a mercapto group, an alkylthio group or an arylthio group group R ⁶ S- (R ⁶ is a lower alkyl group or an aryl group) represented by, formyloxy group, a group R ⁶ COO- ( R ⁶
Is an acyloxy group represented by the same as above), a formyl group, an acyl group represented by a group R ⁶ CO- (R ⁶ is the same as above), and an alkoxy group represented by a group R ⁶ O- (R ⁶ is the same as above) group or an aryloxy group, a carboxy group, group R ⁶ OCO- (R ⁶ is as defined above) such as an alkoxycarbonyl group or an aryloxycarbonyl group represented by may be mentioned. Further, the aryl group or the nitrogen-containing aromatic heterocyclic group for R ⁴ may be a group selected from the above substituents
It may be substituted with one or more same or different kinds of substituents.

In the present invention, in producing the allenyl β-lactam compound represented by the general formula (1) used as a starting material, the azetidinone derivative represented by the general formula (3) is mixed with a base in an appropriate solvent. Let react. In this reaction, the base used is preferably an aliphatic amine or an aromatic amine, and specifically, triethylamine, diisopropylamine, ethyldiisopropylamine, tributylamine, 1,5-diazabicyclo [4.3.0] nonene- 5 (DBN), 1, 8-
Diazabicyclo [5.4.0] undecene-7 (DB
U), 1,4-diazabicyclo [2.2.2] octane (DABCO), piperidine, N-methylpiperidine,
Examples thereof include 2,2,6,6-tetramethylpiperidine, morpholine, N-methylmorpholine, N, N-dimethylaniline, and N, N-dimethylaminopyridine.
The amount of the base to be used is generally 1 to 12 moles, preferably 1 to 6 moles, per mole of the compound of the formula (3). As the solvent, conventionally known solvents can be widely used as long as they dissolve the compound of the formula (3) and are inactive under the conditions of the reaction. Examples thereof include methyl formate, ethyl formate, propyl formate and butyl formate. Lower alkyl esters of lower carboxylic acids such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, diethyl ether, ethyl propyl ether, ethyl butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether ,
Ethers such as methyl cellosolve and dimethoxyethane,
Cyclic ethers such as tetrahydrofuran and dioxane,
Acetonitrile, propionitrile, butyronitrile,
Nitriles such as isobutyronitrile and valeronitrile,
Substituted or unsubstituted aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, and anisole; halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane, trichloroethane, dibromoethane, propylene dichloride, carbon tetrachloride, and fluorocarbons ,
Pentane, hexane, heptane, aliphatic hydrocarbons such as octane, cyclopentane, cyclohexane, cycloheptane, cycloalkanes such as cyclooctane, dimethylformamide, amides such as dimethylacetamide,
Dimethyl sulfoxide and the like can be mentioned. These may be used alone or as a mixture of two or more. Further, these solvents may contain water as necessary. Such a solvent is used per kg of the compound of the general formula (3),
Usually, about 0.5 to 200 l, preferably about 1 to 50 l are used. The reaction is carried out at a temperature in the range of -70 to 100C, preferably -50 to 50C. The compound of the general formula (1) thus obtained can be obtained as a substantially pure product by performing a usual extraction operation or crystallization operation after completion of the reaction, but it is needless to say that the compound is purified by other methods. It is.

The process of the present invention is carried out by electrolytically reducing the allenyl β-lactam compound represented by the above general formula (1) in an organic solvent in the presence of an organic acid. As the organic solvent used in the above reaction, for example, amides such as dimethylformamide, dimethylacetamide, N-methylformanilide, N-formylmorpholine, and cyclic ethers such as tetrahydrofuran and dioxane alone or two or more kinds It may be used as a mixture, and mainly the above-mentioned organic solvent, and other ordinary solvents, for example,
Methyl formate, ethyl formate, propyl formate, butyl formate,
Methyl acetate, ethyl acetate, propyl acetate, butyl acetate,
Lower alkyl esters of lower carboxylic acids such as methyl propionate and ethyl propionate, diethyl ether,
Ethers such as ethyl propyl ether, ethyl butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, methyl cellosolve, dimethoxyethane, acetonitrile, propionitrile, butyronitrile, nitriles such as isobutyronitrile, valeronitrile, benzene, toluene , Xylene, chlorobenzene, substituted or unsubstituted aromatic hydrocarbons such as anisole, dichloromethane, chloroform, dichloroethane, propylene dichloride, halogenated hydrocarbons such as carbon tetrachloride, pentane, hexane, heptane, octane, etc. Hydrogens, cyclopentane, cyclohexane,
A mixed solvent using cycloalkanes such as cycloheptane and cyclooctane, dimethyl sulfoxide and the like can also be used. A particularly suitable solvent is a mixed solvent containing dimethylformamide or tetrahydrofuran as a main solvent.

In carrying out the electrolytic reduction reaction of the present invention, a supporting electrolyte is added to the reaction system. As the supporting electrolyte, for example, organic acids such as formic acid, acetic acid, chloroacetic acid, dichloroacetic acid, trichloroacetic acid, bromoacetic acid, and trifluoroacetic acid are suitably used. The type and concentration of these organic acids can be appropriately selected depending on other conditions such as the type of the raw material compound (1), the pH value of the organic acid, the applied voltage, and the like. .01-10
It is good to be about wt%, preferably about 0.1 to 5 wt%.

The electrolytic reduction reaction of the present invention can be carried out using either a non-separated single cell or a separated cell in which the positive and negative electrode chambers are separated by a diaphragm. Preferably, cells are used. The electrode used in this reaction can be selected from cathode materials such as zinc, tin, lead, platinum, nickel, palladium, tungsten, and aluminum in consideration of other conditions used in the reaction of the present invention. On the other hand, the anode material is not particularly limited, for example, platinum, carbon, stainless steel, iron oxide, surface-treated titanium, zinc, tin, lead, nickel, palladium,
Tungsten, aluminum and the like can be mentioned.

In the electrolytic reduction reaction of the present invention, for example, lead halides such as lead fluoride, lead chloride, lead bromide and lead iodide, lead nitrate, lead sulfate, lead perchlorate, lead borate, lead carbonate, phosphoric acid Inorganic lead such as lead, aliphatic acetate such as lead acetate, lead oxalate, lead stearate, titanium halide such as titanium fluoride, titanium chloride, titanium bromide, titanium iodide, titanium sulfate, titanium nitrate, etc. Inorganic gallium halides such as inorganic acid titanium, gallium fluoride, gallium chloride, gallium bromide, gallium iodide, etc., inorganic gallium such as gallium sulfate, gallium nitrate, gallium perchlorate, zirconium fluoride, zirconium chloride, zirconium bromide , Zirconium halides such as zirconium iodide, tellurium fluoride, tellurium chloride, tellurium bromide, tellurium halides such as tellurium iodide, bismuth fluoride, bismuth chloride, Bismuth halides of bismuth, such as iodide bismuth, bismuth nitrate, bismuth inorganic acids such as sulfuric acid bismuth, organic bismuth such as bismuth acetate,
Antimony fluoride such as antimony fluoride, antimony chloride, antimony bromide and antimony iodide, rhodium fluoride such as rhodium fluoride and rhodium chloride, rhodium bromide and rhodium iodide, tin fluoride, tin chloride and tin bromide If tin halide such as tin iodide is added to the reaction system, the reaction efficiency and the reaction yield may be improved. The amount of these additives used is not particularly limited, but usually the raw material compound (1)
About 0.01 to 2 equivalents, preferably 0.05 to
It is preferable to use about 1 equivalent.

For the electrolysis of the present invention, any of a potentiostatic electrolysis method and a galvanostatic electrolysis method can be employed. However, it is preferable to employ a galvanostatic electrolysis method particularly in view of simplicity of the reaction operation. The current density is usually in the range of 1 to 500 mA / cm ² , preferably ² to 50 mA / cm ² .
The amount of electricity passed depends on the shape of the electrolytic cell to be used, the type of the raw material compound (1), the type of the solvent to be used, and the like, and cannot be unconditionally determined.
It is good to be about 10F, preferably about 2-5F.
The electrolysis temperature is not fixed depending on the structures of the raw material compound (1) and the target compound (2), but is preferably in a range of about -100 to 50C, usually in a range of -20 to 40C.

After the completion of the electrolytic reaction, the intended 2-exomethylenepenam derivative (2) can be isolated by subjecting the electrolytic solution to a usual extraction operation. If further purification is necessary, conventional purification means such as a recrystallization method and a column chromatography method may be employed.

The 2-exomethylene penum derivative (2) of the present invention is useful as an intermediate for synthesizing penam antibiotics. For example, the 2-exomethylene penam derivative (2) can be derived into a 2-substituted methyl penam derivative represented by the general formula (6) according to the method shown in the following reaction formula-1.

[Reaction formula-1]

[0028]

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Wherein R ¹ , R ² and R ³ are as defined above.
Y represents a nucleophile residue. ]

[0030]

Next, the method of the present invention will be described in more detail by way of examples, but the present invention is not limited to the following examples.

Reference Example 1

[0032]

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1 g of the compound (3a) [R ¹ = phenylacetamide, R ² = H, R ³ = diphenylmethyl, X = phenylsulfonyl, R ⁵ = trifluoromethyl]
Dissolve in 10 ml of N-dimethylformamide. After cooling to −30 ° C., triethylamine 0.43
Then, the mixture was stirred at -30 ° C for 1 hour to react. The reaction mixture was extracted with ethyl acetate, and the extract was washed with water and dried over anhydrous sodium sulfate. When the extract is concentrated under reduced pressure,
Compound (1a) [R ¹ , R ² , R ³ and X are as defined above] is obtained in a yield of 99%.

NMR (CDCl ₃ ); δ ppm 3.61 (s, 2H), 5.31 (dd, 1H, J = 5)
Hz and 7 Hz), 5.57 and 5.70 (ABq, 2
H, J = 15 Hz), 5.84 (d, 1H, J = 5H)
z), 6.02 (d, 1H, J = 7 Hz), 6.81
(S, 1H), 7.22-7.73 (m, 20H).

Reference Examples 2 to 8 Using the starting compounds shown in Table 1, the same reaction as in Reference Example 1 was carried out to obtain the following compounds.

[0036]

[Table 1]

The following summarizes the NMR data.

NMR (CDCl ₃ ); δ ppm Compound (1b): 3.58 (s, 2H), 3.80
(S, 3H), 5.10 (s, 2H), 5.32 (d
d, 1H, J = 5 Hz and 8 Hz), 5.60 and 5.
47 (ABq, 2H, J = 15 Hz), 5.87 (d,
1H, J = 5 Hz), 6.08 (d, 1H, J = 8H)
z), 6.85-7.83 (m, 14H) Compound (1c): 3.59 (s, 2H), 3.74
(S, 3H), 5.33 (dd, 1H, J = 5 Hz and 8 Hz), 5.54 and 5.64 (ABq, 2H, J =
5.15 Hz), 5.88 (d, 1H, J = 5 Hz), 6.
02 (d, 1H, J = 8 Hz), 7.20-7.90
(M, 10H) Compound (1d): 3.67 (s, 2H), 5.25 (d
d, 1H, J = 5 Hz and 8 Hz), 5.69 (d, 1
H, J = 5 Hz), 5.60 and 5.76 (ABq, 2
H, J = 15 Hz), 6.71 (s, 1H), 7.00
-7.34 (m, 20H) Compound (1e): 3.02 (dd, 1H, J = 2.6H)
z and 15.7 Hz), 3.58 (dd, 1H, J =
5.4 Hz and 15.7 Hz), 3.79 (s, 3
H), 5.17 (s, 2H), 5.47 and 5.60.
(ABq, 2H, J = 15.2 Hz), 5.62 (d
d, 1H, J = 2.6 Hz and 5.4 Hz), 6.87
-7.89 (m, 9H) Compound (1f): 2.99 (dd, 1H, J = 2.6H)
z and 15.7 Hz), 3.53 (dd, 1H, J =
5.5 Hz and 15.7 Hz), 5.56 (dd, 1
H, J = 2.6 Hz and 5.5 Hz), 5.54 and 5.66 (ABq, 2H, J = 15.2 Hz), 6.8
8 (s, 1H), 7.29-7.76 (m, 15H).

Reference Examples 9 to 11 The reaction was carried out in the same manner as in Example 1 except that the reaction solvent and the reaction temperature were changed as shown in Table 2, to obtain the compound of the general formula (1a) in the yield shown in Table 2. Was.

[0040]

[Table 2]

Embodiment 1

[0042]

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Compound (1b) was placed in a test tube having an inner diameter of 15 mm.
[R ¹ = phenylacetamide, R ² = H, R ³ = p-
Methoxybenzyl, X = phenylsulfonyl] 50 mg
And dissolve in 5 ml of dimethylformamide. While stirring this solution, 100 μl of trifluoroacetic acid is added. A zinc electrode (2.0 × 1.0 cm ² ) was
A constant current electrolysis of 10 mA is performed by mounting the sheets. 140 minutes,
After passing a current of 10 F / mol, the reaction solution was diluted with ethyl acetate.
Extract with 2% hydrochloric acid. The organic layer is washed with aqueous sodium hydrogen carbonate and water in that order, and then dried over sodium sulfate. The obtained organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the desired 2-exomethylene penam derivative (2b) [R ¹ ,
R ² and R ³ are the same as described above) with a yield of 67%.

NMR (CDCl ₃ ); δ ppm 3.61 (ABq, 2H, J = 16 Hz), 3.80
(S, 3H), 5.11 (s, 2H), 5.18 (t,
1H, J = 1 Hz), 5.24 (t, 1H, J = 1H)
z), 5.35 (t, 1H, J = 1 Hz), 5.57
(D, 1H, J = 4 Hz), 5.75 (dd, 1H, J
= 4 Hz and 9 Hz), 6.07 (d, 1H, J = 9H)
z), 6.85-7.40 (m, 9H).

Embodiment 2

[0046]

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Bismuth chloride 5 m in a test tube with an inner diameter of 15 mm
g and compound (1b) [R ¹ = phenylacetamide,
R ² = H, R ³ = p-methoxybenzyl, X = phenylsulfonyl] 50 mg, and dimethylformamide 5
Dissolve in ml. While stirring this solution, 100 μl of trifluoroacetic acid is added. A zinc electrode (2.0
× 1.0 cm ² ) and perform 10 mA constant current electrolysis. After applying a current of 3 F / mol for 42 minutes, the reaction solution is extracted with ethyl acetate-2% hydrochloric acid. The organic layer is washed with aqueous sodium bicarbonate and water in that order, and then dried over sodium sulfate. The obtained organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the desired 2-exomethylene penum derivative (2b) [R ¹ , R ² and R ³ were the same as above. The same was obtained in a yield of 75%.

Examples 3 to 5 Example 2 was repeated except that the electrode material was changed as shown in Table 3.
The target product (2b) was obtained in the yield shown in Table 3.

[0049]

[Table 3]

Examples 6 and 7 The reaction was carried out in the same manner as in Example 2 except that the indicator electrolyte was changed to the organic acid shown in Table 4 instead of trifluoroacetic acid, and the target compound (2b) was obtained in the yield shown in Table 4. I got

[0051]

[Table 4]

Examples 8 to 11 The reaction was carried out in the same manner as in Example 2 except that the additives were changed to the compounds shown in Table 5 instead of bismuth trichloride, and the target compound (2b) was obtained in the yield shown in Table 5. I got

[0053]

[Table 5]

Examples 12 to 14 The reaction was carried out in the same manner as in Example 1 except that the reaction solvent was changed to the solvents shown in Table 6 instead of dimethylformamide.
The target product (2b) was obtained in the yield shown in Table 6.

[0055]

[Table 6]

Embodiment 15

[0057]

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Using 50 mg of the compound (1a) [R ¹ = phenylacetamide, R ² = H, R ³ = diphenylmethyl, X = phenylsulfonyl] as a starting material, the same reaction as in Example 2 was carried out to obtain the compound (2a) [R ¹ , R
² and R ³ are the same as described above) in a yield of 72%.

NMR (CDCl ₃ ); δ ppm 3.62 (S, 2H), 5.26-5.28 (m, 2
H), 5.37 (t, 1H, J = 2 Hz), 5.61
(D, 1H, J = 4 Hz), 5.76 (dd, 1H, J
= 4 Hz and 9 Hz), 6.14 (d, 1H, J = 9H)
z), 6.82 (s, 1H), 7.20-7.41
(M, 15H).

Embodiment 16

[0061]

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Compound (1e) [R ¹ = R ² = H, R ³ =
p-methoxybenzyl, X = phenylsulfonyl] 50
Using mg as a starting material, the same reaction as in Example 2 was carried out, and a compound (2e) (R ¹ , R ² and R ³ were the same as above) was obtained in a yield of 68%.

NMR (CDCl ₃ ); δ ppm 3.16 (dd, 1H, J = 1.5 Hz and 16H
z), 3.66 (dd, 1H, J = 4 Hz and 16H
z), 3.82 (s, 3H), 5.13 (s, 2H),
5.24 (dd, 1H, J = 1.8 Hz and 1.8H
z), 5.28 (dd, 1H, J = 1.8 Hz and 1.28).
8 Hz), 5.32 (dd, 1H, J = 1.8 Hz1.
8 Hz), 5.38 (dd, 1H, J = 1.5 Hz and 4 Hz), 6.87-7.30 (m, 4H).

Embodiment 17

[0065]

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Compound (1f) [R ¹ = R ² = H, R ³ =
Diphenylmethyl, X = phenylsulfonyl] 50 mg
Using as a starting material, the same reaction as in Example 2 was carried out to obtain a compound (2f) (R ¹ , R ² and R ³ are the same as above) in a yield of 74%.

NMR (CDCl ₃ ); δ ppm 3.12 (dd, 1H, J = 1.5 Hz and 16.0 H)
z), 3.60 (dd, 1H, J = 4.1 Hz and 1
6.0 Hz), 5.23 (dd, 1H, J = 1.8 Hz)
And 1.8 Hz), 5.32 (dd, 1H, J = 1.8).
Hz and 1.8 Hz), 5.36 (dd, 1H, J =
1.5 Hz and 4.1 Hz), 5.37 (dd, 1H,
J = 1.8 Hz and 1.8 Hz), 6.87 (s, 1
H), 7.27-7.35 (m, 10H).

[0068]

According to the present invention, the desired 2-exomethylenepenam derivative represented by the general formula (2) can be obtained in a simple operation, in an industrially advantageous manner, and in a high yield and a high yield. Manufactured in purity.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI C25B 3/04 // C07D 205/08 (72) Inventor Takashi Shiro 463 Kasuno, Kawauchi-cho, Tokushima City, Tokushima Prefecture Otsuka Chemical Co., Ltd. Tokushima Research In-house (72) Inventor Yutaka Kameyama 24-19-406 Okudahonmachi, Okayama City, Okayama Prefecture (56) References JP-A-4-282387 (JP, A) JP-A-5-97864 (JP, A) JP-A-4 −283583 (JP, A) Synlett, No. 12, 888-890, (1991) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 499/00 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A compound of the general formula [In the formula, R ¹ represents a hydrogen atom, a halogen atom, an amino group or a protected amino group. R ² represents a hydrogen atom, a halogen atom, a lower alkoxy group, a lower acyl group, a lower alkyl group, a lower alkyl group having a hydroxyl group or a protected hydroxyl group as a substituent, a hydroxyl group or a protected hydroxyl group. Alternatively, R ¹ and R ² may combine with each other to form an oxo group. R ³ represents a hydrogen atom or a carboxylic acid protecting group. X is a group -SO ₂ R ⁴ or a group -SR ^4. Here, R ⁴ represents an aryl group which may have a substituent or a nitrogen-containing aromatic heterocyclic group which may have a substituent. ]
The electrolytic reduction of an allenyl β-lactam compound represented by the general formula Wherein R ¹ , R ² and R ³ are the same as above. A method for producing a 2-exomethylene penum derivative represented by the formula: