JPH05148187A - New cyclobutane derivative and its production - Google Patents

Abstract

PURPOSE:To obtain the subject derivative useful as a synthetic intermediate for carbooxetanosine G, etc., to be expected as an antiviral agent. CONSTITUTION:A derivative of formula I [R1 and R2 are H or OH-protecting group; X is NCO or COOR3 (R3 is H or 1-4C alkyl)] such as (1alpha (beta), 2alpha; 3beta)-2,3- bis(benzyloxymethyl)-1-cyclobutylcarboxylic acid methyl ester. The compound of formula I is obtained by treating a compound of formula III obtained from a compound of formula II as a starting raw material with light rays using a lamp having >=300nm wavelength (preferably 300-580nm) and >=200W (preferably >=400W) output in a solvent such as methanol at 0-80 deg.C (preferably 20-40 deg.C) for 1-8 hours (preferably 2-5 hours).

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel cyclobutane derivative and a method for producing the same.

[0002]

2. Description of the Related Art A nucleic acid-related substance having an antiviral action or an anticancer action is represented by the following formula (A)

[0003]

[Chemical 4]

The compound represented by the formula (1) is known, and this compound is expected as a drug. (JP-A-2-6478, JP-A-3-95165)

[0005]

DISCLOSURE OF THE INVENTION The present invention provides a novel cyclobutane derivative expected as an important intermediate in the synthesis of the compound represented by the above formula (A) and a process for producing the same.

The present invention has the general formula (1)

[0006]

[Chemical 5]

[Wherein, R ₁ and R ₂ each independently represent a protector for a hydrogen atom or a hydroxyl group, X is —NCO or —COOR ₃ (R ₃ is a hydrogen atom or a C ₁ -C ₄ lower alkyl group) Represents an oxycarbonyl group. ] The new cyclobutane derivative represented by these. And 2) general formula (2)

[0008]

[Chemical 6]

[Wherein R ₁ and R ₂ are the same as those defined above], and light is allowed to act on the compound represented by the general formula (1a).

[0010]

[Chemical 7]

[Wherein R ₁ , R ₂ and R ₃ are the same as above]
The present invention relates to a method for producing a novel cyclobutane derivative represented by

In the general formulas (1), (1a) and (2), the hydroxyl-protecting group is not particularly limited as long as it is generally used as a protector, and an ester-type protecting group,
For example, an acyl group such as an acetyl group or a benzoyl group, or an ether type protecting group, for example, a substituted silyl group such as a tert-butyldimethylsilyl group or a tert-butyldiphenylsilyl group, or a (C ₁ -C ₄ alkoxy group such as a methoxymethyl group. ) C
₁ -C ₄ alkyl group, cyclic acetal groups such as tetrahydropyranyl group, or a benzyl group, 4-methoxybenzyl group, and a least one methyl group substituted by a substituted or unsubstituted phenyl group such as a trityl group. General formula (1),
In (1a), the lower alkyl group is methyl,
Examples thereof include ethyl, propyl and tert-butyl groups.

To obtain a compound of the general formula (1a) in which X in the general formula (1) is —COOR ₃ , the general formula (2)
It suffices that light is applied to the compound. An example of the reaction that causes this light to act is the wolff rearrangement reaction. Specifically, in an alcohol such as methanol, ethanol or butanol, water, or a mixed solvent of the alcohol or water with a chemically or photochemically inert solvent such as acetone, ethyl acetate, tetrahydrofuran, DMF or acetonitrile. 0 ° C-80 ° C, preferably 20 ° C-
Wavelength 300 nm or more at 40 ° C., preferably 300 to 58
Light with a lamp having an output of 200 W or more, preferably 400 W or more at 0 nm is applied for 1 to 8 hours, preferably 2 to
The compound of general formula (2) may be allowed to act for 5 hours. When this reaction is carried out in the presence of alcohol, a compound in which R ₃ is alkyl is obtained, and when this reaction is carried out in the presence of acid or alkali and water, a compound in which R ₃ is H is obtained. Further, a compound in which R ₃ is H is a compound in which R ₃ is an alkyl, in a solvent such as water or an alcohol such as methanol, sodium hydroxide, potassium hydroxide, or a hydroxide such as lithium hydroxide, potassium carbonate or carbonate. It can also be obtained by causing an alkali metal carbonate such as sodium to act and hydrolyze by a conventional method.

When it is desired to obtain one of the isomers of the compound represented by the general formula (1), it may be separated by chromatography or the following method.

[0015]

[Chemical 8]

Further, among the compounds represented by the general formula (I), when it is desired to obtain an optically active substance, a compound represented by the general formula (I) produced as a racemate and a carboxylic acid wherein X is --COOH From diastereomeric salts obtained by mixing with various amines such as optically active amines, each diastereomer is isolated by chromatography, crystallization, etc., and each diastereomer is decomposed to give optically active carbohydrates. It may be produced as an optically active substance by introducing an acid or by using an optically active raw material.

The compound in which X in the general formula (1) is --NCO can be obtained by subjecting the compound (R ₃ = H) of the general formula (1a) obtained by the above method to Schmidt rearrangement, Lofsen rearrangement, Hoffmann rearrangement and Curtius rearrangement. By rearrangement reaction such as
Obtainable. The Schmid rearrangement is carried out by using a reagent such as sodium azide in a solvent such as sulfuric acid or polyphosphoric acid represented by the formula (1
In the compound of a), 1 to 2 equivalents of 30 to
It is allowed to act at 60 ° C. for 5 to 10 hours, and then the obtained acid azide is added to 100 to 1 in an inert solvent such as benzene or toluene.
It may be heated at 20 ° C. for 1 to 3 hours. Lofsen rearrangement is
For example, in a solvent such as sulfuric acid or polyphosphoric acid, 1 to 2 equivalents of vidroxylamine are added at 150 to 170 ° C., preferably 16
It may be allowed to act at 0 to 165 ° C for 10 to 30 minutes. In this case, not only a compound in which X in the general formula (1) is —NCO but also a compound in which —NH ₂ is further hydrolyzed is obtained. The Hoffman rearrangement is, for example, the general formula (1a)
The compound (R ₃ = H) of ( ₃ ) is converted into an acid amide derivative by a conventional method, that is, oxalic acid chloride, thionyl chloride or the like is reacted to form an acid chloride. This acid amide derivative may be reacted with 4 to 6 equivalents of sodium hydroxide and 1 to 1.2 equivalents of bromine in water and heated at 75 to 80 ° C. for 10 to 30 minutes. In this case, a compound in which X in the general formula (1) is —NH ₂ can be obtained as in the case of the Rossen rearrangement. The Curtius rearrangement is carried out by adding a base such as chloroformate and triethylamine to a compound of the formula (1) in a solvent such as acetone and tetrahydrofuran in an amount of 2 to 3 equivalents 0-1 respectively.
After operating at 0 ° C. for 30 to 60 minutes to form a mixed acid anhydride, 3 to 4 equivalents of sodium azide are added at that temperature and reacted for 30 to 60 minutes. Then, the obtained acid azide is added in an insoluble solvent such as benzene or toluene to 100 to 12
It may be heated at 0 ° C. for 1 to 3 hours. The production route of the compound of the present invention is exemplified as follows.

[0018]

[Chemical 9]

[Chemical 10]

In the above production route, the starting compound 1 is a known compound ("Journal of American Chemical Society", vol. 107, 3343).
P.-3345, 1985). To obtain the compound of the above formula (A) using the compound of the present invention as a raw material, for example, an isocyanate in which X is —NCO in the formula (1) is treated under an alkaline condition such as sodium hydroxide, lithium hydroxide or hydrous pyridine, or diluted hydrochloric acid. Then, it is decomposed into an amine by decomposing it under acidic conditions such as dilute sulfuric acid or hydrous acetic acid, and then the amine portion is converted to guanine by a known method (JP-A-3-2154).
86, JP-A-3-240788).

EXAMPLES Next, the production of the compound of the present invention will be specifically described with reference to Examples.

Example 1. Compound 2 ((3α, 4β)-
Synthesis of 3,4-bis (hydroxymethyl) -1-cyclopentylidene) In a 1000 ml four-necked flask, under argon atmosphere, 17.4 g (0.458 mol) of lithium aluminum hydride was suspended in 200 ml of anhydrous THF to prepare a mixture of 5 to 10 parts. C was cooled.
Next, 200 ml of an anhydrous THF solution containing 67.5 g (0.151 mol) of Compound 1 was added dropwise, and the mixture was reacted for 1 hour. At the end of the reaction, ethanol (about 200 ml), water (about 200 ml)
Was sequentially added until foaming stopped, and the generated precipitate was filtered and washed using Celite or the like. 20 times the obtained filtrate
After concentrating to 0 ml, extraction with 600 ml of ether was carried out in 3 portions, and the ether layer was extracted with 1N-HCl, water and saturated NaH.
CO ₃ water and brine were washed in this order, dried over sodium sulfate, and concentrated to obtain a residue (53.0 g). Purification is performed by silica gel chromatography. (Si
O ₂ : 600 g hexane / ethyl acetate = 1/1 → 1 /
6), and 212.41 g of the compound was obtained (yield: 57.6).
%).

IR (film): 3300, 2920, 16
55, 1035, 875 (cm ^-1 ) ¹ H-NMR (400MHZ, CDCl ₃ ) δ: 1.97 (2H, bs)
1.99 (2H, m) 2.48 (2H, m) 3.41 (2H, m) 3.7
5 (2H, m) 4.82 (2H, bs) 3.3-
3.8 (2H (OH): bs) ¹³ C-NMR (400MHZ, CDCl ₃ ) δ: 36.4, 48.0, 6
6.1, 105.9, 148.9

Example 2. Compound 3 ((3α, 4β)-
Synthesis of 3,4-bis (benzyloxymethyl) -1-cyclopentylidene) 12.7 g (0.318 mol) of sodium hydride (60% wet) in a 1000 ml four-necked flask under an argon atmosphere.
Was suspended in 100 ml of anhydrous DMF, and 100 ml of a solution of 11.61 g (0.0814 mol) of Compound 2 in anhydrous DMF was added dropwise with stirring at room temperature. After the bubbling of hydrogen gas disappeared, 100 ml of an anhydrous DMF solution containing 48.0 g of benzyl bromide was added dropwise at room temperature, and the mixture was further stirred overnight. After completion of the reaction, after adding 30 ml of methanol and 500 ml of water,
1000 ml of ether was extracted 4 times, and the organic layer was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure to obtain 58 g of a residue. Purification is performed by silica gel chromatography (SiO ₂ 15
0 g, hexane / ethyl acetate = 20/1), compound 3
23.8 g was obtained (yield: 90.7%).

IR (film): 2860, 1660, 150
0, 1100, 875, 740, 700, (cm ⁻¹ ) ¹ H-NMR (400MHZ, CDCl ₃ ) δ: 2.15 (bs, 2H)
2.16 (m, 2H) 2.53 (m, 2H) 3.35 (m, 2H) 3.51 (m, 2H) 4.49 (s, 4H) 4.82 (m, 2H) 7. 25-7.37 (m, 10H)

Example 3. Compound 4 ((3α, 4β)
Synthesis of -3,4-bis (benzyloxymethyl) -1-cyclopentanone 12.6 g (0.039) of compound 3 in a 500 ml flask.
mol), THF (65 ml) and water (100 ml) were added and the mixture was vigorously stirred at room temperature. Next, a solution of osmium tetroxide in t-butanol (OsO ₄ 1.08 / 15 ml) 6.3 ml (1.64 mmo)
l) and sodium periodate 22.5 g (0.105 m
ol) was added and the reaction was carried out for 6 hours. After completion of the reaction, 200 ml of ethyl acetate was added, and the white precipitate was filtered using Celite, and the precipitate was thoroughly washed with 200 ml of ethyl acetate. The collected organic layer was washed with a ZN-NaOH aqueous solution, further washed with water and saturated saline, dried over sodium sulfate, and concentrated under reduced pressure to obtain 13.2 g of a residue. Purification is performed by silica gel column chromatography (Si
O ₂ 460 g-hexane / ethyl acetate = 4/1) and compound 4 18.6 g were obtained (yield 78.3%).

IR (film): 2850, 1735, 149
5, 1450, 1400, 1362, 1090, 73
5,695 (cm ^-1 ) ¹ H-NMR (400MHZ, CDCl ₃ ) δ: 2.16 (2H, m) 2.44 (2H, bs) 2.44 (2H, m) 3.51 (4H, m) 4.50 (4H, s) 7.25 to 7.35 (10H, Complex)

Example 4. Compound 5 ((3α, 4β)
-2-diazo-3,4-bis (benzyloxymethyl)
Synthesis of -1-cyclopentanone) In a 200 ml two-necked flask under an argon atmosphere, 10 ml of absolute ethanol and 430 mg (0.019 mol) of sodium metal.
l) was added, and after dissolution, the mixture was concentrated to dryness under reduced pressure. The obtained white powder was suspended in 100 ml of anhydrous THF, and 3.56 g (0.011 mol) of an anhydrous THF solution of Compound 4 under ice cooling was used.
ml was added dropwise over 40 minutes, and after the completion of the addition, 10 ml of an anhydrous THF solution containing 2.1 g (0.022 mol) of ethyl formate was added, and the mixture was stirred for 3 hours. After the reaction is complete, add 100 ml of water to the reaction mixture.
And the by-product was extracted with 200 ml of ethyl acetate.
The pH of the aqueous layer was slowly adjusted to 6 with 1N-HCl water under ice cooling.
Neutralized until ~ 7. The liberated oily substance was extracted with 300 ml of diethyl ether (divided into 3 portions), washed with saturated saline, dried over sodium sulfate, and further concentrated under reduced pressure to obtain 3.72 g of a brown oily substance. 3.72 g of the obtained oil was dissolved in 50 ml of anhydrous methylene chloride,
Triethylamine (3.6 ml, 0.025 mol) and paratoluenesulfonic acid azide (2.38 g, 0.012 mol) were added, and the mixture was stirred at room temperature-medium night. After completion of the reaction, dilute with 100 ml of methylene chloride and wash with water and brine in this order.
The organic layer was dried over sodium sulfate and further concentrated under reduced pressure to obtain about 6.5 g of an oily residue. Purification is performed by silica gel column chromatography (SiO ₂ 250
g, hexane / ethyl acetate = 3/1), yellow compound 5
3.07 g was obtained (yield 79.6%).

IR (film): 2860, 2080, 166
7, 1450, 1300, 1097, 735, 700
^{(Cm -1) 1 H-NMR} (400MHZ, CDCl 3) δ: 2.23 (dd, J = 1
9.5, 6.8, 1H) 2.24 (m, 1H) 2.54 (dd, J = 19.5, 10.8, 1H) 3.44 (m, 2H) 3.51 (m, 2H) 3.80 (m, 1H) 4.51 (s, 2H) 4.53 (s, 2H) 7.2-7.4 (m, 10H)

Example 5- (1) (1α (β), 2α,
3β) -2,3-bis (benzyloxymethyl) -1-
Synthesis of methyl cyclobutylcarboxylate (compound 6a) (3α, 4β) -2-diazo-3,4-bis (benzyloxymethyl) -1-cyclopentanone (compound 5)
2000 ml of methanol solution of 6.0 g (17.13 mol)
Was placed in a 2000 ml flask, thoroughly degassed and replaced with argon, and then a high pressure mercury lamp (400 W pyrex filter)
While maintaining the bath temperature at 30 to 40 ° C., light irradiation was performed until the raw material disappeared. After completion of the reaction, the reaction solution was concentrated under reduced pressure,
The obtained residue is purified by silica gel column chromatography to obtain (1α (β), 2α, 3β)-
5.04 g (14.22 mmol) of methyl 2,3-bis (benzyloxymethyl) -1-cyclobutylcarboxylate was obtained (yield 83.0%). 1α: 1β = about 1: 1 IR ν (film): 2870, 1730, 1170, 7
40, 700

Example 5-2 (1α (β), 2α, 3
Synthesis of tert-butyl β) -2,3-bis (benzyloxymethyl-1-cyclobutylcarboxylate) (Compound 6b) (3α, 4β) -2-diazo-3,4-bis (benzyloxymethyl) -1 -Cyclopentanone (Compound 5)
500 g of tertBUOH solution of 1.2 g (3.41 mmol) was put into a 1000 ml flask, and after deaeration and purging with argon, a high pressure mercury lamp (400 W Pyrex filter) was used.
While maintaining the bath temperature at 30 to 40 ° C., light irradiation was performed until the raw material disappeared. After completion of the reaction, the reaction solution was concentrated under reduced pressure,
The residue was purified by silica gel column chromatography to obtain 0.96 g (2.42 mmol) of tert-butyl (1α (β), 2α, 3β) -2,3-bis (benzyloxymethyl) -1-cyclobutylcarboxylate. Obtained (yield 71.0%). 1α = 1β: about 1: 1 IR (film): 2850, 1720, 1363, 125
0, 1210, 1150, 735, 695 (cm ^-1 )

Example 6. (1α (β), 2α, 3β)
Synthesis of 2,3-bis (benzyloxymethyl) -1-cyclobutylcarboxylic acid (Compound 2) (1α (β), 2α, 3β) -2,3-bis (benzyloxymethyl) -1-cyclobutyl 30 ml of a methanol solution of 5.00 g (14.11 mmol) of methyl carboxylate (compound 6a) was placed in a 500 ml flask, 230 ml of a methanol solution of 9.3 g of potassium hydroxide (165.8 mmol) was added, and the mixture was allowed to stand at room temperature for 22 hours. The mixture was stirred at 45 ° C for 4 hours. After the reaction was completed, the reaction solution was concentrated to a half volume under reduced pressure, and 300 ml of water and 200 ml of ether were added for extraction.
The aqueous layer was neutralized with dilute hydrochloric acid, and the liberated carboxylic acid was extracted with 200 ml of ethyl acetate (× 2 times), washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure to give compound 7 4.
81 g (yield 100%) was obtained. IR (film): 2500-3300, 1702, 145
0, 740, 700 (cm ^-1 )

Example 7. (1α (β), 2α-3β)
Synthesis of 2,2,3-bis (benzyloxymethyl) -1-cyclobutylisocyanate (Compound 8) 100 ml flask (1α (β), 2α, 3β) -2,3
-Bis (benzyloxymethyl) -1-cyclobutylcarboxylic acid (Compound 7) (111.3 mg, 0.33 mmol) and 4 ml of acetone were added, and triethylamine, 3 was added under ice cooling.
9.7 mg (0.39 mmol) and chlorocarbonic acid, ethyl 4
6.1 mg (0.43 mmol) was added and after stirring for 1 hour, an aqueous solution of sodium azide 31.9 mg (0.49 mmol) 1.
5 ml was added dropwise. After the reaction was completed, it was diluted with 10 ml of cold water and extracted twice with 10 ml of diethyl ether. The ether layer was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure to give 106.3 mg of oily acid azide. The obtained oily substance was dissolved in 7 ml of anhydrous toluene without purification,
Heat on an oil bath at 80-90 ° C for 1 hour. After cooling, the mixture was concentrated under reduced pressure to give compound 8 (106.9 mg, 0.33 mol)
(Yield: 100%) was obtained. IR (film): 2860, 2270, 1100, 74
0, 700 (cm ^-1 )

Example 8. (1α (β), 2α, 3β)
-2,3-Bis (hydroxymethyl) -1-cyclobutylcarboxylic acid (Compound 9) (1α (β), 2α, 3 parts) -2,3-bis (benzyloxymethyl) -1-cyclobutylcarboxylic acid 100 ml of 4.8 g (14.11 mmol) of (Compound 7) was added, and 500 ml of methanol and 0.9 g of 10% palladium carbon were added. Then, the mixture was vigorously stirred under a hydrogen atmosphere at normal pressure and room temperature for 4 hours. After completion of the reaction, the catalyst was filtered off and the filtrate was concentrated to dryness to obtain 2.25 g of the desired compound 8 (15.05).
mmol) was obtained (yield 99.6%). IR (film): 3400, 2950, 1750, 116
5,1040 (cm ^-1 )

Example 9. Synthesis of Compounds 10a and 10b (1α (β), 2α, 3β) -2,3-bis (hydroxymethyl) -1-cyclobutylcarboxylic acid (Compound 9)
1.50 g (9.37 mmol) was placed in a 100 ml flask, anhydrous DMF 28 ml, paratoluene sulfonic acid 190
mg and molecular sieves 4A 2.0g,
Stir vigorously for 2 days at room temperature. After confirming the formation of compound (10b; lactone form) by TLC, acetic anhydride 7.5 ml (about 80 mmol) and pyridine 12.8 ml (about 1)
(60 mmol) was added, and the mixture was further stirred at room temperature for 4 hours. After completion of the reaction, neutralize with saturated aqueous sodium hydrogen carbonate solution (pH
= 8-9) and then extracted twice with 100 ml of ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure to give 1.7 g of an oily substance. Purification was carried out by silica gel column chromatography, compound 1
276.5 mg (1.50 mmol) of 0b (lactone form) was obtained (yield 32.1%).

IR (film): 2960, 1770, 17
40, 1250, (cm ^-1 ) ¹ H-NMR (400MHZ, CDCl ₃ ) δ: 2.08 (3H, s) 2.29 (1H, d, J = 6.83Hz) 2.30 (1H, d , J = 6.35 Hz) 2.70 (1H, m) 2.99 (1H, dd, J = 6.35, 13.2 Hz) 3.07 (1H, ddd, J = 0.98, 6.35) 1
3.2 Hz) 4.12 (2H, m) 4.27 (1H, dd, J = 0.98, 9.77 Hz) 4.37 (1H, dd, J = 6.35, 9.77 Hz)

Further, the aqueous layer was neutralized with 6N-hydrochloric acid (pH = 3-4) under ice cooling, and the liberated carboxylic acid was extracted twice with 100 ml of ethyl acetate and washed with water and saturated saline. After drying over sodium sulfate and concentrating under reduced pressure, 1.12 g of crude residue
Got Purification was carried out by silica gel chromatography to obtain 1.06 g (4.36 mm) of the desired compound 10a.
ol) got. (Yield 93.1%).

IR (film): 3200, 2960, 17
35, 1712, 1240 (cm^-1) ¹ H-NMR (400MHZ, CDCl₃) δ: 2.00 (1H, m) 2.07 (3H, s) 2.08 (3H, s) 2.28 (1H, m) 2.40 (1H, m) 2.68 (1H, m) ) 2.90 (1H, m) 4.0 to 4.2 (4H, Complex)

Example 10. (1β, 2β, 3α)-
Synthesis of 2,3-bis (acetoxymethyl) -1-cyclobutylisocyanate (Compound 11) (1β, 2β, 3α) -2,3-bis (acetoxymethyl) -1-cyclobutylcarboxylic acid (Compound 10a)
20 0.62 g (2.54 mmol) and 40 ml of acetone
The mixture was placed in a 0 ml flask, 0.44 ml (3.18 mmol) of triethylamine and 0.34 ml (3.56 mmol) of ethyl chlorocarbonate were added and reacted for 1 hour while stirring under ice cooling. Then, an aqueous solution of 267 mg of sodium azide 3.0
ml was added and the reaction was continued for 7 hours. The extraction was carried out in the same manner as in Example 7 to obtain 0.62 g of acid azide, which was dissolved in 10 ml of anhydrous toluene without purification, heated at 80 ° C. for 30 minutes and concentrated to dryness to give 0 0.58 g (2.40 mmol) was obtained (yield 94.
7%).

IR (film): 2965, 2270, 17
40, 1240, (cm ^-1 ) ¹ H-NMR (400MHZ, CDCl ₃ ) δ: 1.77 (1H, m) 2.07 (1H, m) 2.08 (3H, s) 2.09 (3H , S) 2.42 (2H, m) 3.69 (1H, m) 4.04 (1H, dd, J = 6.35, 11.23H
z) 4.10 (1H, dd, J = 5.37, 11.23H
z) 4.12 (2H, d, J = 5.86Hz)

Claims (2)

[Claims] 1. A general formula (1): [In the formula, R ₁ and R ₂ each independently represent a hydrogen atom or a hydroxyl-protecting group, and X is —NCO or —COOR.
₃ (R ₃ represents a hydrogen atom or a C ₁ -C ₄ lower alkyl group). ] The new cyclobutane derivative represented by these. 2. A general formula (2): (In the formula, R ₁ and R ₂ each independently represent a hydrogen atom or a hydroxyl-protecting group.) The compound represented by the general formula (1a): [Wherein R ₁ and R ₂ are the same as above, R ₃ is a hydrogen atom or C
Preparation of novel cyclobutane derivatives represented by ₁ -C shows a ₄ lower alkyl group]