JPH0881439A - Azetidinone compound and its production - Google Patents

Abstract

PURPOSE: To obtain an azetidinone compound using a not expensive raw material useful as an intermediate of a compound having an antimicrobial activity with easy handling and operation by reacting individually specific azetidinone derivative and an imide compound in the presence of a specific metallic compound and a base. CONSTITUTION: This aimed compound expressed by formula I (R is H or a removable protecting group; R<1> is a (protected) OH or a (substituted) alkyl; R<2> is a (substituted) alkyl; R<3> and R<4> are each a (substituted) alkyl or a (substituted) aryl; X is O or S) (e.g. N- (R)-2-[(3S,4R)-3-[(R)-1-t- butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-o-chloro-N-i sopropyl- benzamide) is obtained by reacting an azetidinone derivative expressed by formula II and an imide compound of formula III in the presence of a compound of formula IV (M is a metal atom; Hal is a halogen; R is a lower alkyl, etc.; (n) and (m) are each 0 or 1-5; (n+m) is valence of M) and a base.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an azetidinone compound which is a useful synthetic intermediate for a carbapenem compound, a process for producing the same, and use thereof.

[0002]

2. Description of the Related Art As a synthetic intermediate for carbapenem compounds, a compound of the general formula [V ']

[0003]

Embedded image

(In the formula, r is a hydrogen atom or a protecting group which can be easily removed, r ¹ is a hydroxyl group which may be protected or an alkyl group which may be substituted with a halogen atom, and r ² is substituted. Represents an optionally substituted alkyl group.)
The carboxylic acid derivative represented by is important, and several production methods thereof have been proposed. Among them, JP-A-62-2527
General formula [VI] for No. 86

[0005]

[Chemical 9]

(In the formula, r ¹ and r ² have the same meanings as described above, r represents a hydrogen atom or a protecting group for N which can be easily removed, and r ⁵ is adjacent to an optionally substituted 2 X'is an oxygen atom, a sulfur atom, SO, SO ₂ or Nr ⁶ (r ⁶ is a hydrogen atom, an alkyl group or a phenyl group).
Y'represents an oxygen atom, a sulfur atom, or Nr ⁷ (r ⁷ represents a hydrogen atom, an alkyl group or a phenyl group). ]
It is described that the 4-substituted azetidinone represented by the formula (4) is easily hydrolyzed to a carboxylic acid derivative represented by the general formula [V '].

[0007] In addition, Tetrahedron Let
t. Vol. 27 5687-5690 (1986) in general formula [VII]

[0008]

[Chemical 10] (In the formula, X ′ has the same meaning as described above, and r ⁸ and r ⁹
Each represents a hydrogen atom or a methyl group. ) Is shown.

However, these general formulas [VI] and [VII]
] The 4-substituted azetidinone derivative represented by the above formula is not industrially suitable because it is produced using expensive boron triflate or tin triflate.

In addition, WO 93/13064 (PCT /
JP92 / 01698), a general formula [II ']

[0011]

[Chemical 11] (In the formula, r ′ represents a hydrogen atom or a protecting group which can be easily removed, r ′ ¹ represents a hydroxyl group which may be protected or an alkyl group which may be substituted with a halogen atom, and z ′ represents a leaving group. ) And an azetidinone derivative represented by the general formula [III ′]

[Chemical 12] (Wherein, r ^'2 is a hydrogen atom, an alkyl group, r' ³ is an alkyl group, trialkylsilyl group, an alkyl group, an alkoxy group, a nitro group or an optionally substituted phenyl group with a halogen atom, a cycloalkyl Group, naphthyl group,
Anthracenyl group, a fluorenyl group, a benzothiazolyl group, a naphthalimidyl group, r ^'4 is or r represents an electron withdrawing group' to form a ring ³ and r ^'4 together. ) Is a compound represented by the general formula [IV ′] Ti (Cl) n (Or ′ ⁵ ) m [IV ′] (in the formula, r ′ ⁵ represents a lower alkyl group, 0 ≦ n ≦ 4,
0 ≦ m ≦ 4 and n + m = 4. ) In the presence of a compound represented by the formula) and a base, the compound of the general formula [I ′]

[Chemical 13] (In the formula, r ′ represents a hydrogen atom or a protecting group which can be easily removed, r ′ ¹ represents a hydroxyl group which may be protected or an alkyl group which may be substituted with a halogen atom, r ′ ²
Is a hydrogen atom or an alkyl group, and r ′ ³ is an alkyl group, a trialkylsilyl group, an alkyl group, an alkoxy group, a nitro group or a phenyl group which may be substituted with a halogen atom, a cycloalkyl group, a naphthyl group, an anthracenyl group. , Fluorenyl group, benzthiazolyl group, naphthalimidyl group, r ′ ⁴ represents an electron withdrawing group or r ′ ³
And r ^'4 are taken together to form a ring. ) Is shown.

Equation 1

Embedded image Describes that the compound (C) in which the absolute configuration of the carbon at the 2-position of the propionyl moiety is S was obtained as the main product.

[0013]

The present invention provides intermediates of 1β-methylcarbapenem compounds useful as antibacterial agents.

[0014]

Means for Solving the Problems The present inventors have focused on the compound (B) in the formula 1, and since only the non-substituted benzene ring part has been implemented, introduction of a substituent, alkyl group As a result of diligent study of conversion into a substituted benzene compound,
It was found that a compound in which the absolute configuration of the carbon at the 2-position of the propionyl moiety is R is obtained as the main product from an alkyl compound, and the present invention has been completed.

That is, the present invention has the general formula [I]

[Chemical 15] (In the formula, R is a hydrogen atom or a protecting group which can be easily removed, R ¹ is an optionally protected hydroxyl group or an alkyl group which may be substituted with a halogen atom, and R ² is optionally substituted. An alkyl group, R ³ and R ⁴ are the same or different and each represents an optionally substituted alkyl group or a substituted aryl group, X is an oxygen atom or a sulfur atom, provided that R ³ is isopropyl and R ⁴ Is an unsubstituted phenyl group and X is an oxygen atom), a method for producing the same, and a method for using the same.

As the protecting group R for N, a protecting group generally used for protecting N can be used. Specific examples thereof include trisubstituted silyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, triisopropylsilyl, dimethylhexylsilyl, t-butyldiphenylsilyl, dimethylcumylsilyl, and optionally substituted benzyl groups. (Examples of the substituent include a nitro group and a lower alkoxy group.), A lower alkoxycarbonyl group, a halogeno lower alkoxycarbonyl group, and an optionally substituted benzyloxycarbonyl group (the substituents are a nitro group and a lower alkoxy group. And the like), and an acyl group such as an acetyl group and a benzoyl group.

As the hydroxyl-protecting group for R ¹ , a protecting group generally used for protecting a hydroxyl group can be used. Specific examples thereof include trisubstituted silyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, triisopropylsilyl, dimethylhexylsilyl, t-butyldiphenylsilyl, dimethylcumylsilyl, and optionally substituted benzyl groups. (Examples of the substituent include a nitro group and a lower alkoxy group.), A lower alkoxycarbonyl group, a halogeno lower alkoxycarbonyl group, and an optionally substituted benzyloxycarbonyl group (the substituents are a nitro group and a lower alkoxy group. And the like), an acetyl group, an acyl group such as a benzoyl group, a triphenylmethyl group, a tetrahydropyranyl group, and the like.

The alkyl group of R ² is a lower alkyl group having 1 to 5 carbon atoms such as methyl, ethyl, propyl, isopropyl and butyl, and the substituent thereof is
Examples include lower alkoxy groups and halogen atoms.

As the alkyl group for R ³ and R ⁴ , a lower alkyl group having 1 to 12 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, pentyl and hexyl is preferable, and among them, the alkyl group for R ³ is preferably A branched or cyclic alkyl group such as isopropyl, t-butyl, isobutyl, s-butyl, neopentyl, cyclohexyl and the like, and a substituent thereof include a phenyl group, a lower alkoxy group, a halogen atom and the like.

Examples of the aryl group of R ³ and R ⁴ include a phenyl group, a naphthyl group and an anthracenyl group.
Examples of the substituent include halogen atoms such as fluorine, chlorine and bromine, lower alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl and t-butyl, methoxy, ethoxy and propoxy. Examples include lower alkoxy groups, phenyl groups, alkylthio groups, substituted amino groups, nitro groups, cyano groups and the like.

The leaving group for Z is linear, branched or cyclic alkanoyloxy, aroyloxy optionally having a monocyclic or bicyclic heteroatom, arylalkanoyloxy, alkylsulfonyloxy, arylsulfonyloxy, carbamoyl. Oxy, alkoxycarboxy, aralkoxycarboxy, acyloxy groups such as alkoxyalkanoyloxy, alkanoylthio, acylthio groups such as aroylthio, alkylsulfinyl, sulfinyl groups such as arylsulfinyl, alkylsulfonyl, sulfonyl groups such as arylsulfonyl, fluorine,
Examples thereof include halogen atoms such as chlorine and bromine.

Examples of the base include secondary and tertiary amines and pyridines. Examples thereof include alkylamines such as dimethylamine, diethylamine, diisopropylamine and dicyclohexylamine, alkylanilines such as N-methylaniline, piperidine, and the like. Pyrrolidine, 2,2
Secondary amines such as heterocyclic amines such as 6,6-tetramethylpiperidine, morpholine and piperazine, alkylamines such as diisopropylethylamine, diisopropylmethylamine and triethylamine, dialkylanilines such as N, N-dimethylaniline, 1 -Ethylpiperidine, 1-methylmorpholine, 1-ethylpyrrolidine,
1,4-diazabicyclo [2,2,2] octane, 1,
Heterocyclic amines such as 8-diazabicyclo [5,4,0] -7-undecene or tertiary amines such as diamines such as N, N, N ', N'-tetramethylethylenediamine, α, β or γ-picoline, 1,2-, 2,4
-, 2,5-, 2,6-, 3,4-, 3,5-lutidine, alkyl pyridines such as 2,4,6-collidine, dialkyl pyridines such as dimethylaminopyridine, condensed heterocycles such as quinoline Examples thereof include pyridines such as cyclized pyridine.

In the production of the compound represented by the general formula [I], the reaction is a chlorine-based solvent such as methylene chloride or chloroform, an aromatic solvent such as chlorobenzene or toluene, an organic solvent such as a polar solvent such as acetonitrile, Alternatively, in these mixed solvents, an enolate is formed with an imide compound represented by the general formula [III] and a metal compound represented by the general formula [IV] and an amine, aniline or pyridine, and the enolate and the general formula [ II] is reacted with the azetidinone derivative. This reaction is carried out at -50 ° C. to 10 ° C. for both formation of enolate and reaction of enolate with azetidinone derivative
It is preferably carried out at 0 ° C., especially −20 ° C. to 50 ° C.

An imide compound represented by the general formula [III],
The amount of the metal compound represented by the general formula [IV] and the base used is appropriately 1 to 4 mol per 1 mol of the azetidinone derivative represented by the general formula [II].

The compound represented by the general formula [I] can be converted into the carboxylic acid derivative represented by the general formula [V] by hydrolysis.

[0026]

Embedded image

This hydrolysis reaction can be carried out by a conventional method. For example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide in a suitable solvent in the presence of hydrogen peroxide or It is carried out by using in the absence. As the solvent, for example, alcohols such as methanol and ethanol, an organic solvent such as acetone, tetrahydrofuran, dioxane and dimethylformamide, and a mixed solvent of water are used. The amount of the alkali metal hydroxide used is 1 mol of the compound represented by the general formula [I].
1 to 8 mol, preferably 2 to 4 mol. When hydrogen peroxide is used, the amount used is 1 to 8 mol, especially 2
-4 mol is preferred. The reaction temperature is -10 to 80.
° C, especially 0-40 ° C is preferred. After the completion of the reaction, the target product can be obtained by performing usual post-treatment.

The compound represented by the general formula [III] is, for example, a compound represented by the general formula

[Chemical 17] (In the formula, R ³ and R ⁴ are the same or different and each represents an optionally substituted alkyl group or an optionally substituted aryl group, and X represents an oxygen atom or a sulfur atom). Compounds and general formula

[Chemical 18] (In the formula, R ² represents an optionally substituted alkyl group, and Y represents a halogen atom such as chlorine or bromine.) Or a compound represented by the general formula

[Chemical 19] (Wherein R ² and R ³ have the same meanings as described above) and the general formula

Embedded image (Wherein R ⁴ and X have the same meanings as described above, and Z represents a halogen atom such as chlorine and bromine) in a suitable solvent (for example, a halogen-based solvent such as methylene chloride). , An ester solvent such as ethyl acetate, a hydrocarbon solvent such as toluene, an ether solvent such as tetrahydrofuran, acetonitrile, dimethylformamide and the like), a deoxidizing agent (for example, an organic base compound such as triethylamine and pyridine, sodium hydride, t -Potassium butoxide,
-50 in the presence of sodium hydroxide, potassium carbonate, etc.)
It can be produced by reacting at a temperature of from ℃ to the boiling point of the solvent, preferably from -20 to 90 ° C.

[0029]

EXAMPLES Next, the present invention will be described in more detail by way of examples. Example 1 N-{(R) -2-[(3S, 4R) -3-[(R)-
1-t-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionyl} -o-chloro-N-isopropylbenzamide

[Chemical 21] 6.45 g of titanium tetrachloride was added dropwise to a solution of 8.12 g of o-chloro-N-isopropyl-N-propionylbenzamide in 80 ml of methylene chloride at 0 ° C. Next, 4.14 g of diisopropylethylamine was added dropwise at the same temperature, and then (3R, 4R) -4-acetoxy-3-[(R)
5.75 g of -1-t-butyldimethylsilyloxyethyl] azetidin-2-one was added at 10 ° C. The reaction mixture was stirred at 20 to 25 ° C for 1.5 hr, poured into cold water, and the methylene chloride layer was washed with water. The methylene chloride layer was dried over anhydrous magnesium sulfate, and methylene chloride was distilled off.
Crystals precipitated by adding n-hexane to the residue were collected by filtration and recrystallized from ethyl acetate-n-hexane to give white crystals 7.43.
g was obtained. m. p. 146-148 ° C

Example 2 N-{(R) -2-[(3S, 4R) -3-[(R)-
1-t-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionyl} -N-cyclohexyl-p-methylbenzamide

[Chemical formula 22] 4.72 g of titanium tetrachloride was added dropwise at 0 ° C. to a solution of 6.40 g of N-cyclohexyl-p-methyl-N-propionylbenzamide in 60 ml of methylene chloride. Next, after adding 2.37 g of triethylamine dropwise at the same temperature,
(3R, 4R) -4-acetoxy-3-[(R) -1-
t-Butyldimethylsilyloxyethyl] azetidine-2
4.20 g of ONE was added at 10 ° C. 2 reaction mixtures
After stirring at 0 to 25 ° C for 1.5 hours, the mixture was poured into cold water and the methylene chloride layer was washed with water. The methylene chloride layer was dried over anhydrous magnesium sulfate, and methylene chloride was distilled off. Crystals precipitated by adding n-hexane to the residue were collected by filtration and recrystallized from ethyl acetate-n-hexane to obtain 3.50 g of white crystals. The mother liquor was collected and concentrated, and the residue was purified by silica gel column chromatography to obtain another 1.6 g. m. p.
158-161 ° C

Examples 3-10 Corresponding N-propionylbenzamide compounds and (3
R, 4R) -4-acetoxy-3-[(R) -1-t-
Butyldimethylsilyloxyethyl] azetidin-2-one was treated in the same manner as in Examples 1 and 2 to obtain the compounds shown in Table 1 below.

[0032]

[Chemical formula 23]

[0033] ¹ H NMR data (CDCl ₃ ) of the compound of Example 4
δ (ppm): 7. (2H; d), 7.5 (2H;
d), 6.3 (1H; brs), 4.5 (1H; m),
4.1 (1H; m), 3.8 (1H; m), 2.9 (1
H, m), 2.7 (1H; m), 1.4 (6H; d),
1.1 (3H; d), 1.0 (3H; d), 0.9 (9
H; s), 0.1 (3H; s), 0.0 (3H; s)

Example 11 N-{(R) -2-[(3S, 4R) -3-[(R)-
1-t-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionyl} -N-isopropyl-o-methoxybenzamide

[Chemical formula 24] To a solution of 4.30 g of N-isopropyl-o-methoxy-N-propionylbenzamide in 40 ml of methylene chloride, 4.01 g of zirconium tetrachloride was added dropwise at 0 ° C. Next, after adding 2.22 g of diisopropylethylamine at the same temperature, (3R, 4R) -4-acetoxy-3-
[(R) -1-t-butyldimethylsilyloxyethyl]
3.10 g of azetidin-2-one was added at 10 ° C.
After stirring the reaction mixture at 20-25 ° C. for 1.5 hours,
It was poured into cold water and the methylene chloride layer was washed with water. The methylene chloride layer was dried over anhydrous magnesium sulfate, and methylene chloride was distilled off. Crystals precipitated by adding n-hexane to the residue were collected by filtration and recrystallized from ethyl acetate-n-hexane to obtain 2.50 g of white crystals.

Example 12 N-{(R) -2-[(3S, 4R) -3-[(R)-
1-t-Butyldimethylsiloxyethyl] -2-oxoazetidin-4-yl] propionyl} -N-isopropyl-propionamide

[Chemical 25] To a solution of 3.4 g of N-isopropyl-N-propionylpropionamide in 50 ml of methylene chloride, 4.1 g of titanium tetrachloride was added dropwise at 5 ° C. Next, 2.5 g of diisopropylethylamine was added dropwise at the same temperature, and then (3R,
3.8 g of 4R) -4-acetoxy-3-[(R) -1-t-butyldimethylsilyloxyethyl] azetidin-2-one were added at 10 ° C. 20-25 reaction mixture
After stirring at ℃ for 1.5 hours, it was poured into cold water and the methylene chloride layer was washed with water. The methylene chloride layer was dried over anhydrous magnesium sulfate, and methylene chloride was distilled off. Crystals precipitated by adding n-hexane to the residue were collected by filtration and recrystallized from ethyl acetate-n-hexane to obtain 2.8 g of white crystals. m. p. 91-92 ° C

Example 13 (R) -2-[(3S, 4S) -3-[(R) -1-t
-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionic acid

[Chemical formula 26] The compound of Example 1, N-{(R) -2-[(3S, 4
R) -3-[(R) -1-t-butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionyl} -o-chloro-N-isopropylbenzamide 0.48 g in water / methanol mixed solvent (2 : 1, 10m
0.3 g of 30% hydrogen peroxide solution was added to the suspension of 1) at room temperature. Then, 0.29 g of 28% aqueous sodium hydroxide solution was added dropwise at the same temperature, and the mixture was further stirred for 1 hour. After completion of the reaction, 10 ml of water was added and washed with methylene chloride, and then the aqueous layer was acidified by adding a 35% hydrochloric acid aqueous solution. Precipitated crystals were collected by filtration, washed with water and dried well to give white crystals 0.25
g was obtained. Target (R) -2-[(3S, 4S) -3-[(R) -1-] from NMR, 1R spectrum and HPLC
It was confirmed to be t-butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionic acid.

Example 14 N-{(R) -2-[(3S, 4R) -3-[(R)-
1-t-butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionyl} -2,6-dichloro-N-isopropylbenzamide

[Chemical 27] To a solution of 9,22 g of 2,6-dichloro-N-isopropyl-N-propionylbenzamide in 130 ml of methylene chloride, a solution of 6.07 g of titanium tetrachloride in 5 ml of methylene chloride was added dropwise at 0 to 5 ° C, and then at the same temperature. Then, a solution of 4.14 g of diisopropylethylamine in 5 ml of methylene chloride was added dropwise. The temperature was raised to 20 ° C, and 4.60 g of (3R, 4R) -4-acetoxy-3-[(R) -1-t-butyldimethylsilyloxyethyl] azetidin-2-one was added. After stirring the reaction mixture at 25-30 ° C. for 2 hours,
The mixture was poured into cold water, the methylene chloride layer was washed with water, dried over anhydrous magnesium sulfate, and methylene chloride was distilled off under reduced pressure. N- in the residue
Hexane was added, the crystals were collected by filtration, and recrystallized from toluene to obtain 6.3 g of white crystals. m. p. 188-192 ° C

Example 15 N-{(R) -2-[(3S, 4R) -3-[(R)-
1-t-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionyl} -o-chloro-N-cyclohexylbenzamide

[Chemical 28] To a solution of o-chloro-N-cyclohexyl-N-propionylbenzamide (8.0 g) in methylene chloride (70 ml), titanium tetrachloride (5.24 g) was added dropwise at 0 to 5 ° C, and then diisopropylethylamine (3.24 g) was added dropwise at the same temperature. did. The temperature was raised to 25 ° C., and 4.97 g of (3R, 4R) -4-acetoxy-3-[(R) -1-t-butyldimethylsilyloxyethyl] azetidin-2-one was added. The reaction mixture was stirred at 28 to 32 ° C for 0.5 hr, poured into cold water, the methylene chloride layer was washed with water and dried over anhydrous magnesium sulfate, and methylene chloride was distilled off under reduced pressure. N-Hexane was added to the residue, and the crystals were collected by filtration and recrystallized from toluene-n-hexane to obtain 5.3 g of white crystals. m. p. 136-137 ° C

Example 16 N-{(R) -2-[(3S, 4R) -3-[(R)-
1-t-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propionyl} -p-chloro-N-cyclohexylbenzamide

[Chemical 29] To a solution of 17.6 g of p-chloro-N-cyclohexyl-N-propionylbenzamide in 120 ml of methylene chloride, 12.1 g of titanium tetrachloride was added dropwise at 0 to 5 ° C, and then 7.5 g of diisopropylethylamine was added at the same temperature. did. The temperature was raised to 25 ° C., and 11.5 g of (3R, 4R) -4-acetoxy-3-[(R) -1-t-butyldimethylsilyloxyethyl] azetidin-2-one was added. The reaction mixture was stirred at 28 to 32 ° C for 0.5 hr, poured into cold water, the methylene chloride layer was washed with water and dried over anhydrous magnesium sulfate, and methylene chloride was distilled off under reduced pressure. N-Hexane was added to the residue, and the crystals were collected by filtration and recrystallized from toluene-n-hexane to obtain 9.8 g of white crystals. m. p. 148-150 ° C

Reference Example 1 o-chloro-N-isopropyl-N-propionylbenzamide

[Chemical 30] 10.0 g of o-chloro-N-isopropylbenzamide
Was added to 100 ml of toluene, and then 6.1 g of propionyl chloride was added. The mixture was heated to 70 ° C., and 6.66 g of triethylamine was added dropwise at the same temperature. The mixture was further stirred at the same temperature for 2 hours, and after confirming the completion of the reaction, it was cooled to room temperature. After water was added to the reaction mixture for washing, toluene was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 12.58 g of a colorless oily substance. ¹ HNMR (CDCl ₃ ; δppm): 1.07 (3
H, t), 1.41 (6H, d), 2.52 (2H,
q), 4.23 (1H, m), 7.33 to 7.45 (4
H, m)

[0041]

The compound of the present invention has antibacterial activity.
(R) -2-[(3S, 4S) -3-, which is useful as an intermediate for the production of β-methylcarbapenem compounds and is a general-purpose intermediate for 1β-methylcarbapenem compounds.
[(R) -1-t-Butyldimethylsilyloxyethyl]
It can be easily converted to 2-oxoazetidin-4-yl] propionic acid. Further, the production of the compound of the present invention is an inexpensive raw material and is easy to handle and operate, which is advantageous as an industrial production method.

Claims (9)

[Claims] 1. A compound represented by the formula [I]: (In the formula, R is a hydrogen atom or a protecting group which can be easily removed, R ¹ is an optionally protected hydroxyl group or an alkyl group which may be substituted with a halogen atom, and R ² is optionally substituted. The alkyl group, R ³ and R ⁴ are the same or different and each represents an optionally substituted alkyl group or an optionally substituted aryl group, and X represents an oxygen atom or a sulfur atom, provided that R ³ is An azetidinone compound represented by isopropyl, R ⁴ is an unsubstituted phenyl group and X is an oxygen atom.). 2. A formula [II]: (Wherein R represents a hydrogen atom or a protecting group that can be easily removed, R ¹ represents a hydroxyl group which may be protected or an alkyl group which may be substituted with a halogen atom, and Z represents a leaving group). Azetidinone derivatives represented by the general formula [II
I] [Chemical 3] (In the formula, R ² represents an alkyl group which may be substituted,
³ , R ⁴ are the same or different and each represents an optionally substituted alkyl group or an optionally substituted aryl group, and X represents an oxygen atom or a sulfur atom. However, the case where R ³ is isopropyl, R ⁴ is an unsubstituted phenyl group, and X is an oxygen atom is excluded. ) And an imide compound represented by the general formula M (Hal) n (R ⁵ ) m [IV] (wherein M is a metal atom, Hal is a halogen atom, R
⁵ is a lower alkyl group, a lower alkoxy group, a phenoxy group, a substituted phenoxy group, or a cyclopentadienyl group, n and m are 0, 1, 2, 3, 4 or 5, and n + m is a valence of M Indicates. ) The compound represented by the general formula [I] (In the formula, R, R ¹ , R ² , R ³ , R ⁴ and X are the same as the above.) A method for producing an azetidinone compound. 3. The method according to claim 2, wherein M is Ti or Zr and m + n is 4. 4. The method according to claim 2, wherein M is Al and m + n is 3. 5. A compound represented by the general formula [I]: (Wherein R, R ¹ , R ² , R ³ , R ⁴ and X have the same meanings as described above) and hydrolyze an azetidinone compound represented by the general formula [V] 6] (In the formula, R, R ¹ and R ² have the same meanings as described above.) A method for producing a compound represented by the formula. 6. R ⁴ is a halogen atom, a lower alkyl group,
The compound according to claim 1 or 2, which is a benzene ring substituted with 1 to 5 groups selected from a lower alkoxy group, a nitro group and an aryl group, and a method for producing the same. 7. The compound according to claim 1, wherein R ³ is a branched or cyclic alkyl group selected from isopropyl, t-butyl, cyclohexyl, neopentyl, isobutyl, s-butyl or a benzyl group and its production. Method. 8. The compound according to claim 1 or 2, wherein X is oxygen, and the process for producing the same. 9. A compound of the general formula [II] is represented by: (Wherein A represents a hydrogen atom or a hydroxyl-protecting group, and Z represents the same meaning as described above), and the compound and the method for producing the same.