JP2717117B2 - 4- (2-ethynyl-2-cyclopentenylidene) -2-butyne derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial application] The present invention relates to a novel compound, 4- intermediate, which is useful as an intermediate for producing the antitumor antibiotic neocarzinostatin and its derivatives.
It relates to a (2-ethynyl-2-cyclopentenylidene) -2-butyne derivative.

[Conventional technology]

Neocarzinostatin, an antitumor antibiotic, is already used in gastric cancer,
It is widely used in clinical practice as a therapeutic agent for pancreatic cancer, acute leukemia and the like. This neocarzinostatin has a molecular weight
It is composed of 11000 protein parts and NCS-C with a molecular weight of 659. NCS-C is responsible for its antitumor activity, and has the following structure [Tetrahedron Letters, 26, 331, 1985].

[Problems to be Solved by the Invention] However, it is known that NCS-C is extremely unstable against heat and light (Japanese Patent Publication No. 60-30679). Therefore, the development of analogs and derivatives of NCS-C that are stable against heat, light, etc. has been demanded, and the present inventors have made various studies and have previously conducted bicyclo [8.3.0] trideca-9,13-diene. Patent application for -2,7-diyne derivative (Japanese Patent Application No. 1-47150)
issue〕.

Accordingly, stable intermediates of NCS-C and bicyclo [8.3.0] tridec-9,13-dinene-2,7-diyne derivatives have been required.

[Means for solving the problem]

The present inventor has conducted intensive research in view of the above circumstances,
4- (2-ethynyl-2- represented by the following general formula (I)
(Cyclopentenylidene) -2-butyne derivative was successfully synthesized, and found to be useful as an intermediate for the production of NCS-C and the like, thus completing the present invention.

That is, the present invention provides the following general formula (I) [Wherein, R ¹ represents a hydrogen atom or an organic silyl group, and R ² represents a halogenomethyl group, a hydroxymethyl group, an organic silyloxymethyl group, an acyloxymethyl group, or an acyl group]. (Ethynyl-2-cyclopentenylidene) -2-butyne derivatives.

The 4- (2-ethynyl-2-cyclopentenylidene) -2-butyne derivative of the present invention is a compound represented by the above formula (I), wherein the organic silyl group of R ¹ is, for example, trimethylsilyl, Examples thereof include trialkylsilyl groups such as triethylsilyl and tripropylsilyl groups, and examples of the halogenomethyl group for R ² include chloromethyl and bromomethyl groups. Examples of the organic silyloxymethyl group for R ² include those in which the organic silyl is trimethylsilyl, triethylsilyl, and tripropylsilyl.Examples of the acyloxymethyl group include those in which acyloxy is acetoxy, propionyloxy, butyryloxy, and the like. Examples of the acyl group include formyl, acetyl, propionyl, naphthoyl, anthranyl and the like.

The compound (I) of the present invention is a novel compound and can be produced, for example, by the method shown in the following formula.

That is, 2-bromo-2-cyclopenten-1-one (2) is reacted with 2-cyclopentenone (1) with bromine and the like, and 2-bromo-1- (2) is reacted with propargyl bromide and the like. -Propynyl) -2-cyclopenten-1-ol (3) is obtained. This (3)
Is dissolved in tetrahydrofuran (hereinafter referred to as "THF") or the like, and a Grignard reagent, an aldehyde or the like is added and reacted to obtain 2-bromo-1- (4-hydroxy-2-butynyl).
-2-cyclopenten-1-ols (4). This (4) is reacted with an organic silyl compound such as a trialkylsilylacetylene to give (5), and then the organic silyl group is removed to give (6). If (6) is dehydrated using an acid halide, the present invention can be achieved. Compound (Ia) is obtained.

Further, the above (4) is reacted with an organic silyl compound such as a trialkylsilyl chloride to obtain (7), and then reacted with a trialkylsilylacetylene or the like to obtain (8), which is further reacted with THF, acetic acid, or the like. The compound (Ib) of the present invention can be obtained by converting the organic silyloxy group to a hydroxyl group (5), converting the resulting group to an acyl group using acetic anhydride or the like (10), and then dehydrating with an acid halide. Furthermore (1
The compound (Ic) of the present invention can be obtained by removing the organic silyl group in (0) with a tetraalkylammonium fluoride or the like (11) and then dehydrating with an acid halide.

The compound (8) can be converted to the compound (Id) of the present invention by dehydration with an acid halide, and the compound (Id) of the present invention can be converted to a hydroxyl group by using an organic silyloxy group using THF, acetic acid or the like.
e) is obtained and further reacted with an alkylsulfonyl halide or the like to obtain the compound (If) of the present invention.

Further, (8) removes the organic silyl group with tetrabutylammonium fluoride or the like to form (12), and reacts the hydroxyl group of (12) with trialkylsilyl halide or the like to form an organic silyloxy group (13). The compound of the present invention (Ig) can be obtained by dehydration using a compound. This to T
The compound of the present invention (Ih) can be obtained by reacting with HF, acetic acid or the like, and the compound of the present invention (Ii) can be obtained by reacting with alkylsulfonyl halide or the like. Compound (Ii) of the present invention can also be obtained by reacting (12) with an alkylsulfonyl halide or the like.

The compound (I) of the present invention obtained as described above is obtained by combining NCS-C and bicyclo [8.3.0] tridec-9,13 as described above.
-Diene-2,7-diyne derivatives are useful as intermediates.

〔Example〕

Next, the present invention will be described in more detail with reference to Reference Examples and Examples, but the present invention is not limited thereto.

Reference Example 1 Production of 2-bromo-2-cyclopenten-1-one (2): 10 ml of 2-cyclopentenone and 120 ml of dichloromethane were stirred at 0 ° C., and a mixture of 6.15 ml of bromine and 120 ml of dichloromethane was added thereto. Was added dropwise over 30 minutes, and the mixture was stirred for 5 minutes. Then, at 0 ° C., 26.6 ml of triethylamine and dichloromethane were added.
120 ml of the mixture is added dropwise over 50 minutes, the temperature is raised to room temperature, and the mixture is stirred for 1.5 hours. Then, an appropriate amount of hexane is added to precipitate a salt. After filtering the salt, the mixture is washed three times with 50 ml of 10% hydrochloric acid, twice with 50 ml of water and once with 100 ml of saturated saline, and dried with magnesium sulfate. The target substance was obtained by removing the solvent and purifying the residue by silica gel column chromatography.

Shape: 17.26 g (yield 89.8%) of yellowish white solid Reference Example 2 Production of 2-bromo-1- (2-propynyl) -2-cyclopenten-1-ol (3): Under an argon atmosphere, 5 ml of anhydrous diethyl ether was added. As a solvent, 226 mg of magnesium is reacted with 0.65 ml of propargyl bromide in the presence of 1 to 2 mg of mercury (II) chloride, and the mixture is heated under reflux for about 10 minutes. After allowing to cool to room temperature, 2-bromo-2
A solution of 933 mg of cyclopenten-1-one in 10 ml of ether is added. Since an oil precipitates, 10 ml of anhydrous tetrahydrofuran is added to make a homogeneous solution. After stirring for 10 minutes, 5 ml of water is added to stop the reaction. Further, 20 ml of water, 10 ml of a saturated aqueous ammonium chloride solution and saturated saline were added, and the mixture was added to ether.
Extract three times with 25 ml. The ether layer was washed with saturated saline (30 ml), dried over anhydrous sodium sulfate, concentrated, and the residue was purified by silica gel column chromatography to obtain the desired product (3).

Form: colorless oil 904 mg (yield 77%) ¹ H-NMR (200 MHz, CDCl ₃ ): δ 2.02 (t, 1 H, J = 2.5 Hz), 2.18 (s, 1 H, —OH), 2.22-
2.52 (m, 4H), 2.55 (dd, 1H, J = 2.5, 16.5Hz), 2.67 (dd,
1H, J = 2.5,16.5Hz), 6.09 (t, 1H, J = 2.5Hz) IR (film): ν3400,3300,2930,2850,1620,1060,940,63
5cm ^-1 Reference Example 3 5.06 g (25.2 mmol) of (3) is placed in a reaction vessel, and the inside is replaced with argon. To this, 25 ml of dry tetrahydrofuran (THF) is added to dissolve (3), and the temperature of the vessel is raised to 50 ° C. 80.3 ml of ethyl Grignard reagent (EtMgBr)
(75.6 mmol) was added, and the mixture was stirred at 50 ° C for about 30 minutes. Then, 3.48 g (75.6 mmol) of formaldehyde was added, and the mixture was stirred at 40 to 50 ° C. The reaction was followed by thin layer chromatography (TLC), and it was confirmed that the reaction was completed after 70 minutes. Then return to room temperature, add 30 ml of saturated ammonium chloride water,
The organic layer was washed and separated. The aqueous layer was extracted three times with 100 ml of ethyl acetate, and the ethyl acetate layer was combined with the previous organic layer, washed with 250 ml of saturated saline, dried over anhydrous MgSO ₄ , and then solvent-removed to obtain a crude product. . This was purified using silica gel column chromatography (SiO ₂ 150 g, hexane / ethyl acetate = 1), and 4.850 g (21.0 mmol) of (4) was obtained as a yellow oil.
l), 83% yield. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 2.0-2.5 (m, 4H), 2.47 (td, 1H, J = 2.0, 16.2 Hz),
2.71 (td, 1H, J = 2.0,16.2Hz), 2.9-3.3 (br, 2H), 4.24
(T, 2H, J = 2.1Hz), 6.06 (t, 1H, J = 2.3Hz) IR (film): ν3340,2928,2855,2220,1617,1425,1322,1
308,1064,1013,968,736cm ^-1 Reference Example 4 In a reaction vessel, 910 mg (4.78 mmol) of CuI and (Ph ₃ P) ₄ Pd1.380
8 g (1.195 mmol) is added, and the inside is replaced with argon. A solution of 5.5308 g (23.934 mmol) of (4), 4.06 ml (28.72 mmol) of trimethylsilylacetylene and 2.84 ml (28.73 mmol) of n-butylamine in 100 ml of dry benzene was added using a cannula, and further 20 ml of benzene was added. And the container was added and stirred. The reaction was followed by TLC, and it was confirmed that (4) had disappeared in 1.5 hours. 50 ml of water was added to the reaction solution, and the organic layer was washed and separated. The aqueous layer was extracted three times with 20 ml of ether, and the ether layer was combined with the previous organic layer, washed with 40 ml of saturated saline, and the saline was extracted twice with 10 ml of ether. The organic layer was dried over anhydrous MgSO ₄ and the solvent was removed to obtain a brown oily crude product. This is repeated three times with silica gel column chromatography (flash SiO ₂ 250 g, hexane / ethyl acetate = 2; SiO ₂ 50
g, hexane / ethyl acetate = 1.5; SiO ₂ 250 g, hexane /
Ethyl acetate = 1.5) purification gave 4.6299 g (18.639 mmol) of (5) as a pale yellow oil in 78% yield. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 0.21 (s, 9H), 1.93-2.11 (m, 1H), 2.21-2.54 (m,
3H), 2.52 (dt, 1H, J = 16.5,2.2Hz), 2.76 (dt, 1H, J = 1
6.5, 2.2Hz), 4.27 (t, 2H, J = 2.2Hz), 6.25 (t, 1H, J = 2.
5Hz) MS (EI, 13.5 eV, 80 ° C): m / z 73 (bp), 179 (21.1%, M ⁺ −
(CH ₂ C≡CCH ₂ OH)) IR (film): ν3356,2962,2906,2852,2148,1425,1319,1
251,1172,1141,1100,1064,1017,959,845,760,700,663,6
42cm ^-1 Reference Example 5 (Method 1) 460.6 mg (1.854 mmol) of (5) was placed in a reaction vessel, and the inside was replaced with argon. To this is added 3 ml of anhydrous THF (5)
Was melted, the vessel was cooled on ice, and 2.0 ml (2.0 mmol) of a THF solution (1.0 M) of tetrabutylammonium fluoride was added dropwise and stirred. The reaction was followed by TLC, and after 3 minutes, it was confirmed that (5) had disappeared. 10 minutes later, add 10 ml of water, and add CH
Extracted 6 times with 10 ml of ₂ Cl ₂ . After drying the organic layer over anhydrous MgSO ₄ , the solvent was removed to obtain a brown oily crude product. This was subjected to flash silica gel column chromatography (SiO ₂ 15
g, hexane / ethyl acetate = 0.5) to obtain 302.3 mg (1.715 mmol) of (6) as a pale yellow oil in a 93% yield.

(Method 2) 302.7 mg (1.219 mmol) of (5) was placed in a reaction vessel, and the inside was replaced with argon. Add 2 ml of anhydrous THF here,
Dissolve (5), cool the container with ice, and add 1.34 ml of a tetrabutylammonium fluoride, (TBAF) THF solution (1.0 M).
(1.34 mmol) was added dropwise and stirred. After 3 minutes by TLC (5)
Was confirmed to have disappeared, and the solvent was removed as it was. After removing the solvent, the residue was immediately subjected to flash silica gel column chromatography (SiO ₂ 15 g, hexane / ethyl acetate = 0.67-
0.5) to give 204.8 mg of pale yellow oil (6)
(1.162 mmol) obtained in 95% yield. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 1.72-1.90 (m, 1H), 2.04-2.37 (m, 3H), 2.36 (d
t, 1H, J = 16.5,2.2Hz), 2.56 (dt, 1H, J = 16.5,2.2Hz),
2.86 (s, 1H), 4.05 (br, t, 2H, J = ~ 2.0Hz), 6.10 (t, 1
H, J = 2.7 Hz) MS (EI, 13.5 eV, 80 ° C.): m / z 107 (bp, M ⁺ − (CH ₂ C≡CCH ₂ O
H)), 108 (7.2%) IR (film): ν3290,2938,2866,2292,2228,2100,1711,1
632,1425,1319,1267,1234,1168,1139,1064,1013,957,92
8,888,857,737,654cm ^-1 Example 1 The inside of the reaction vessel was filled with dry argon, and 0.12 ml (1.38 mmol) of oxalic acid dichloride and 6 ml of anhydrous CH ₂ Cl ₂ were added.
Cooled to -82 ° C. Here, dimethyl sulfoxide (DMS
O) 0.17 ml of (2.39 mmol) of those dissolved in anhydrous CH ₂ Cl ₂ 5ml, was added dropwise over 5 minutes using a Kanyura. After dripping
After stirring for 10 minutes, (6) 165.4 mg (0.9386 mmol) was added to CH ₂
A solution of 5 ml of Cl ₂ was similarly added dropwise over 7 minutes,
Stirred at about -80 ° C for another 20 minutes. Then triethylamine
0.65 ml (4.66 mmol) was added dropwise over 2 minutes.
(The liquid color changed from yellow to red to brown when triethylamine was added.) 5 ml of water was added, the mixture was immediately returned to room temperature, and extracted three times with about 10 ml of CH ₂ Cl ₂ . MgSO ₄
The CH ₂ Cl ₂ layer is dried with, and immediately after the solvent is removed, purified by flash silica gel chromatography (SiO ₂ 15 g, hexane / ethyl acetate = 5-1 → ethyl acetate only) to obtain brown oil (Ia). 31.3 mg (0.200 mmol), 21% yield,
51.0 mg (0.2928 mmol) of pale yellow oil (9) was obtained in a yield of 31%, and 39.7 mg of starting material (6) was obtained in a recovery of 24%.

(Ia): ¹ H-NMR (90 MHz, CDCl ₃ ): δ 2.50-2.78 (m, 2H), 2.7
8-3.03 (m, 2H), 3.19 (s, 1H), 5.81 (brs, 1H), 6.82
(Brt, 1H, J = 2.1 Hz), 9.34 (d, 1H, J = 1.1 Hz) IR (film): ν3286,2922,2850,2166,1651,1599,1581,1
437,1180,998,926,857 cm ^-1 (9); ¹ H-NMR (90 MHz, CDCl ₃ ): δ 1.85-2.34 (m, 2H), 2.3
4-2.75 (m, 2H), 2.84 (d, 1H, J = 16Hz), 2.89 (d, 1H, J
= 16Hz), 3.11 (s, 1H), 6.33 (t, 1H, J = 2.6Hz), 9.16
(S, 1H) IR (film): ν3422,3288,2938,2854,2288,2206,1659,1
390,1323,1141,1064,957,837,658cm- ¹ Reference Example 6 4.65 g (20.1 mmol) of (4) is placed in a reaction vessel, and the inside is replaced with argon. Add 20 ml of pyridine here,
(4) was melted, the vessel was cooled with ice, and 3.88 ml (23.1 mmol) of triethylsilyl chloride was slowly added dropwise thereto, followed by stirring. The reaction was followed by TLC, and it was confirmed that (4) had disappeared after 35 minutes. 30 ml of a saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, and the mixture was returned to room temperature, and the organic layer was washed and dispersed.
The aqueous layer was extracted three times with 30 ml of ether, and the ether layer was combined with the previous organic layer, washed with 50 ml of saturated saline, and dried over anhydrous MgSO _4.
And dried. The solvent was removed while adding 15 ml of benzene three times to obtain a crude product. This was subjected to silica gel column chromatography (SiO ₂ 150 g, hexane / ethyl acetate = 5.8)
6.16 g of (7) as a yellow oil (17.
8 mmol), 89% yield. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 0.64 (dq, 6H, J = 1.8, 8.
0Hz), 0.98 (tt, 9H, J = 0.9, 8.0Hz), 1.2-1.3 (m, 1H),
2.0−2.5 (m, 4H), 2.54 (td, 1H, J = 2.0,16.7Hz), 2.67
(Td, 1H, J = 2.0,16.7Hz), 4.30 (t, 2H, J = 2.2Hz), 6.06
(T, 1H, J = 2.6 Hz) ¹³ C-NMR (200 MHz, CDCl ₃ ): δ 4.4 (t), 6.6 (q), 2
9.8 (t), 30.1 (t), 35.5 (t), 51.4 (t), 80.1
(S), 80.8 (s), 84.2 (s), 127.0 (s), 134.2
(D) IR (film): ν3390, 2940, 2910, 1617, 1465, 1413, 1368, 1
253,1142,1068,1003,734cm ^-1 Reference Example 7 0.13 g (0.683 mmol) of copper iodide (CuI) is placed in a reaction vessel, and the inside is replaced with argon. Here (7) 1.05g
(3.03 mmol) dissolved in 30 ml of anhydrous THF was added using a cannula, and the mixture was stirred at room temperature. 0.57 ml (5.77 mmol) of n-butylamine and 0.61 ml (4.32 mmol) of trimethylsilylacetylene were each dissolved in a syringe, and 0.172 g (0.149 mmol) of (Ph ₃ P) ₄ Pd was dissolved in 10 ml of anhydrous THF. The mixture was added using a cannula and stirred. The reaction was followed by TLC, and it was confirmed that (7) had disappeared in 1.5 hours. 40 ml of a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, and the organic layer was washed and separated. The aqueous layer is 3 with 40 ml of ether
The mixture was extracted twice, and the ether layer was combined with the above organic layer, washed with 100 ml of saturated saline, dried over anhydrous MgSO ₄ , and then subjected to solvent removal to obtain a crude product. This was purified using silica gel column chromatography (SiO ₂ 30 g, hexane / ethyl acetate = 7) to obtain 0.962 g (2.65 mmol) of (8) as a brown oil.
l), 88% yield. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 0.20 (s, 9H), 0.65 (d
q, 6H, J = 1.6,8.1Hz), 0.98 (dt, 9H, J = 1.2,8.1Hz), 1.7
−1.8 (br.s, 1H), 1.9−2.6 (m, 4H), 2.55 (td, 1H, J =
2.0, 16.2Hz), 2.75 (td, 1H, J = 2.0, 16.2Hz), 4.31 (t, 2
H, J = 2.1 Hz), 6.23 (t, 1H, J = 2.5 Hz) ¹³ C-NMR (200 MHz, CDCl ₃ ): δ 4.5 (t), 6.6 (q),
30.3 (t), 30.4 (t), 36.6 (t), 51.5 (t), 80.5
(S), 80.9 (s), 84.8 (s), 98.4 (s), 98.8
(S), 129.9 (s), 140.8 (d) Reference Example 8 Put 101 mg (0.276 mmol) of (8) in the reaction vessel,
0.14 ml of THF, 0.14 ml of water and 0.14 ml of acetic acid were added using a syringe, and the mixture was stirred at room temperature. The reaction was followed by TLC, and it was confirmed that (8) had disappeared after about 2.5 hours. 2 ml of a saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, and the mixture was stirred, and the organic layer was separated. The aqueous layer was extracted three times with 3 ml of ether, and the ether layer was combined with the previous organic layer, washed with saturated saline, dried over anhydrous MgSO ₄ , and then solvent-removed to obtain a crude product. This is subjected to silica gel column chromatography (flash SiO ₂ 10
g, hexane / ethyl acetate = 1.6) to give 67.4 mg (0.271 mmol) of (5) as a yellow oil in 97% yield. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 0.21 (s, 9H), 1.83 (b
rs, 2H), 1.9−2.6 (m, 4H), 2.52 (td, 1H, J = 2.1,17.0H
z), 2.77 (td, 1H, J = 2.1,17.0Hz), 4.26 (t, 2H, J = 1.8H
z), 6.25 (t, 1H, J = 2.7 Hz) IR (film): ν3380, 2990, 2965, 2890, 2157, 1250, 1069, 1
023,862,843,766cm ^-1 Reference Example 9 0.67 g (2.70 mmol) of (5) is placed in a reaction vessel, and the inside is replaced with argon. 2.7 ml of pyridine is added here,
(5) was melted, the container was cooled with ice, and stirred. Thereto was added 0.28 ml (2.97 mmol) of acetic anhydride, and the reaction solution was returned to room temperature and stirred. Follow the reaction by TLC, in about 7 hours (5)
Was confirmed to have disappeared. 3 ml of a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, and the aqueous layer was extracted three times with 3 ml of ether. The organic layer was washed with brine and dried over anhydrous MgSO ₄ . The solvent is removed while adding 10 ml of benzene 5 times,
A crude product was obtained. This was subjected to silica gel column chromatography (flash SiO ₂ 8.2 g, hexane / ethyl acetate =
Purification using 5), 0.71 g of (10) as a yellow oil
(2.44 mmol) in 90% yield. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 0.20 (s, 9H), 1.67 (b
rs, 1H), 2.09 (s, 3H), 1.8-2.6 (m, 4H), 2.54 (td, 1
H, J = 2.0,16.6Hz), 2.77 (td, 1H, J = 2.0,16.6Hz), 4.67
(T, 2H, J = 2.0Hz), 6.24 (t, 1H, J = 2.5Hz) IR (film): ν3452,2964,2852,2244,2148,1746,1437,1
379,1361,1251,1228,1064,1027,963,845,760,735cm- ¹ Example 2 0.118 g (0.41 mmol) of (10) is placed in a reaction vessel, and the inside is replaced with argon. Here is dimethylaminopyridine
A solution prepared by dissolving 0.10 g (0.82 mmol) in 4.1 ml of anhydrous CH ₂ Cl ₂ was added by a cannula, and the mixture was stirred to dissolve (10) and the vessel was cooled with ice. Then, 0.57 ml (4.09 mmol) of triethylamine was added with a syringe, and 0.16 ml of methanesulfonyl chloride was added.
(2.07 mmol) was added dropwise with a syringe over 1 minute.
And stirred. The reaction was followed by TLC, and it was confirmed that (10) had disappeared after 15 minutes. 5 ml of water was added to the reaction solution, the temperature was returned to room temperature, and the organic layer was washed and separated. The aqueous layer is CH ₂ Cl ₂ 5 ml
The mixture was extracted three times, and the CH ₂ Cl ₂ layer was combined with the previous organic layer, washed with a saturated saline solution, dried over anhydrous MgSO ₄ and the solvent was removed to obtain a black-brown crude product. This is repeated twice with silica gel column chromatography (flash SiO ₂ 2.0 g, CH _2
2 Cl ₂ ; flash SiO ₂ 2.0 g, hexane / ethyl acetate = 1
0) Purify, 0.086 g (0.31 g) of (Ib) as a yellow oil
mmol) in a yield of 77%. ¹ H-NMR (200 MHz, CDCl ₃ ): δ 0.21 (s, 9H), 2.11 (s,
3H), 2.54-2.63 (m, 2H), 2.71-2.80 (m, 2H), 4.86
(D, 2H, J = 2.1Hz), 5.64 (br.t, 1H, J = 2.3Hz), 6.56
(T, 1H, J = 3.0Hz) IR (film): ν2962,2216,2160,1752,1620,1582,1379,1
359,1251,1224,1048,1025,845,762cm- ¹ Reference example 10 0.317 g (1.09 mmol) of (10) is placed in a reaction vessel, and the inside is replaced with argon. The container was cooled with ice, and a THF solution (1.0 M) of tetrabutylammonium fluoride was added thereto,
1.20 ml (1.20 mmol) was added dropwise to dissolve (10), and then the container was returned to room temperature and stirred. Follow the reaction with TLC, 3
After 0 minutes, it was confirmed that (10) had disappeared. 2 ml of water was added to the reaction solution, and the organic layer was separated. Water layer ether 2
The mixture was extracted three times with ml, and the ether layer was combined with the previous organic layer, washed with saturated saline, dried over anhydrous MgSO ₄ , and the solvent was removed.
A crude product was obtained. This was subjected to silica gel column chromatography (flash SiO ₂ 6 g, hexane / ethyl acetate = 2.
Purify using 5) to afford 0.206 of (11) as a yellow oil.
g (0.942 mmol) in 86% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 2.08 (s, 3H), 2.58 (td,
1H, J = 2.1,16.4Hz), 2.75 (td, 1H, J = 2.1,16.4Hz), 1.9
−2.6 (m, 4H), 3.05 (s, 1H), 4.66 (t, 2H, J = 2.1Hz),
6.30 (br.s, 1H) IR (film): ν3442,3288,2942,2852,2242,1742,1437,1
381,1363,1232,1064,1027,963,663,607cm- ¹ Example 3 0.289 g (1.32 mmol) of (11) is placed in a reaction vessel, and the inside is replaced with argon. Here dimethylaminopyridine 0.
A solution of 350 g (2.86 mmol) in 14 ml of anhydrous CH ₂ Cl ₂ was added by a cannula, and the mixture was stirred to dissolve (11) and the vessel was cooled with ice. Then, 2.0 ml (13.6 mmol) of triethylamine was added by syringe, and 0.55 ml of methanesulfonyl chloride (7.11
mmol) was added dropwise via syringe over 1 minute and stirred at 0 ° C. The reaction was followed by TLC, and it was confirmed that (11) had disappeared after 15 minutes. 20 ml of water was added to the reaction solution, the temperature was returned to room temperature, and the organic layer was washed and separated. The aqueous layer was extracted 3 times with CH ₂ Cl ₂ 20 ml, and CH ₂ Cl ₂ layer with the previous organic layer was washed with saturated brine, dried over anhydrous MgSO _4, and the solvent was removed, the brown A crude product was obtained. This was repeated twice with silica gel column chromatography (flash SiO ₂ 2.0 g, CH ₂ Cl ₂ ;
Flash SiO ₂ 10 g, hexane / ethyl acetate = 9) Purification, 0.162 g (0.805 mmol) of (Ic) as a reddish brown oil
l), 61% yield. ¹ H-NMR (400 MHz, CDCl ₃ ): δ 2.12 (s, 3H), 2.58-2.
63 (m, 2H), 2.75-2.90 (m, 2H), 3.12 (d, 1H, J = 0.8H
z), 4.86 (d, 2H, J = 2.2Hz), 5.66 (dt, 1H, J = 0.8,2.0H
z), 6.61 (t, 1H, J = 3.1 Hz) IR (film): ν3290, 2920, 2846, 2218, 1748, 1618, 1439, 1
379,1361,1317,1226,1178,1025,1000,967,924,833,646,
607,474,424 cm ^-1 Example 4 0.514 g (1.42 mmol) of (8) is placed in a reaction vessel, and the inside is replaced with argon. Here is dimethylaminopyridine
A solution prepared by dissolving 0.350 g (2.86 mmol) in 14 ml of anhydrous CH ₂ Cl ₂ was added by a cannula, and the mixture was stirred to dissolve (8) and the vessel was cooled with ice. Then, 1.9 ml (13.6 mmol) of triethylamine is added by a syringe, and 0.54 ml of methanesulfonyl chloride is added.
(6.98 mmol) was added dropwise with a syringe over 1 minute.
Stirred at ° C. The reaction was followed by TLC, and after 10 minutes, it was confirmed that (8) had disappeared. 10 ml of water was added to the reaction solution,
After returning to room temperature, the organic layer was washed and separated. CH ₂ Cl ₂ 10
Extract 3 times with ml, combine the CH ₂ Cl ₂ layer with the previous organic layer,
After washing with 30 ml of a saturated saline solution, drying over anhydrous MgSO ₄ and removing the solvent, a crude product was obtained. This was purified using silica gel column chromatography (flash SiO ₂ 15 g, hexane / ethyl acetate = 15) to give a reddish-brown oil (Id)
Was obtained in 0.385 g (1.12 mmol), 79% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 0.22 (s, 9H), 0.65 (q, 6
H, J = 8.1Hz), 0.98 (t, 9H, J = 8.1Hz), 2.4−2.9 (m, 4
H), 4.50 (d, 2H, J = 2.2 Hz), 5.64 (br.s, 1H), 6.52 (b
rt, 1H, J = 2.6Hz) IR (film): ν2960,2920,2880,2155,1367,1248,1163,1
074,1001,857,842,758,746,734,728cm- ¹ Example 5 0.370 g (1.07 mmol) of (Id) was placed in a reaction vessel, and 0.54 ml of THF, 0.54 ml of water, and 0.54 ml of acetic acid were added thereto using a syringe, followed by stirring at room temperature. The reaction was followed by TLC, and it was confirmed that (Id) had disappeared 50 minutes later. 5 ml of a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, and the mixture was stirred, and the organic layer was separated. The aqueous layer was extracted three times with 5 ml of ether, and the ether layer was combined with the organic layer and washed with saturated saline.
After drying over anhydrous MgSO ₄ , the solvent was removed to obtain a crude product. This is subjected to silica gel column chromatography (flash Si
Purification using 12 g of O ₂ and hexane / ethyl acetate = 6) gave 0.212 g (0.92 mmol) of (Ie) as a tan oil.
l), 86% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 0.22 (s, 9H), 2.4-2.9
(M, 4H), 4.45 (br.s, 2H), 5.64 (br.s, 1H), 6.54 (br.
t, 1H, J = 2.8Hz) IR (film): ν3380,2960,2140,1690,1593,1248,1048,1
018,856,843,762,703cm- ¹ Example 6 51 mg (0.22 mmol) of (Ie) is placed in a reaction vessel, and the inside is replaced with argon. 2.2 ml of anhydrous CH ₂ Cl ₂ was added thereto to dissolve (Ie), and the vessel was cooled with ice and stirred. To this, 0.062 ml (0.45 mmol) of triethylamine was added by syringe, and 0.035 ml (0.45 m
mol) was added dropwise over about 1 minute, and the mixture was stirred at 0 ° C. for 1 hour and then at room temperature overnight, and the completion of the reaction was confirmed by TLC. 3 ml of water was added to the reaction solution, and the organic layer was washed and separated. The aqueous layer was extracted 3 times with CH ₂ Cl ₂ 3 ml, and CH ₂ Cl ₂ layer with the previous organic layer, washed with saturated brine, dried over anhydrous MgSO _4, and the solvent was removed, the crude product I got This was purified using silica gel column chromatography (flash SiO ₂ 10 g, hexane / ethyl acetate = 6) to obtain 28 mg (0.11 mmol) of (If) as a yellow oil in a 50% yield.

When this experiment was performed using tosyl chloride in pyridine, ((Ie) 62.3 mg (0.27 mmol), pyridine 0.54 m
l, tosyl chloride 0.082 g (0.43 mmol)) and (If) were obtained, but 8.9 mg (0.024 mmol) and the yield was 9%. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 0.22 (s, 9H), 2.4-2.9
(M, 4H), 4.36 (d, 2H, J = 2.2Hz), 5.64 (br.s, 1H), 6.5
5 ((br.s, 1H) Reference Example 11 108 mg (0.298 mmol) of (8) is placed in a reaction vessel, and the inside is replaced with argon. The vessel was cooled on ice, and a THF solution (1.0 M) of tetrabutylammonium fluoride was added to the vessel with 0.6 ml.
Add 1 ml (0.61 mmol) dropwise, dissolve in (8), and add 0 ° C
And stirred. The reaction was followed by TLC, and it was confirmed that (8) had disappeared after 25 minutes. After 35 minutes, add 3 ml of water to the reaction solution.
Was added and the mixture was returned to room temperature, and the organic layer was separated. The aqueous layer was extracted three times with 3 ml of ethyl acetate, six times with 5 ml of CH ₂ Cl ₂ , and the extraction was repeated while confirming by TLC until (12) was completely extracted from the aqueous layer into the organic layer. The organic layers were combined, washed with saturated saline, and the saline was re-extracted once with 10 ml of CH ₂ Cl ₂ .
After drying the organic layer over anhydrous MgSO ₄ , the solvent was removed to obtain a crude product. This was purified by silica gel column chromatography (flash SiO ₂ 10 g, hexane / ethyl acetate = 0.5) to give 48.3 mg (0.942 mmol) of (12) as a yellow oil.
l), 93% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 1.8-2.8 (m, 4H), 2.57
(Td, 1H, J = 2.0,16.1Hz), 2.75 (td, 1H, J = 2.0,16.1H
z), 3.07 (s, 1H), 4.25 (t, 2H, J = 1.9Hz), 6.30 (t, 1H,
J = 2.6Hz) IR (film): ν3290,2938,2866,2292,2228,2100,1711,1
632,1425,1319,1267,1234,1168,1139,1064,1013,957,92
8,888,857,737,654cm ^-1 Reference example 13 0.481 g (2.75 mmol) of (12) is placed in a reaction vessel, and the inside is replaced with argon. To this, 2.8 ml of pyridine was added, (12) was melted, the vessel was cooled with ice, 0.51 ml (3.04 mmol) of triethylsilyl chloride was added dropwise over 1 minute, and the mixture was stirred. The reaction was followed by TLC, and it was confirmed that (12) had disappeared after 25 minutes. 5 ml of a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, the temperature was returned to room temperature, and the organic layer was washed and separated. The aqueous layer was extracted three times with 7 ml of ether, and the ether layer was combined with the previous organic layer, washed with saturated saline, and dried over anhydrous MgSO _4.
And dried. The solvent was removed while adding 10 ml of benzene three times to obtain a crude product. This was purified using silica gel column chromatography (flash SiO ₂ 10 g, hexane / ethyl acetate = 3.5) to give (13) as a yellow oil.
0.755 g (2.61 mmol) was obtained in a 95% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 0.65 (q, 6H, J = 8.0 Hz),
0.96 (t, 9H, J = 8.0Hz), 1.60 (br, 1H), 1.9-2.6 (m, 4
H), 2.58 (td, 1H, J = 2.1, 16.4 Hz), 2.73 (td, 1H, J = 2.
1,16.4Hz), 3.04 (s, 1H), 4.30 (t, 2H, J = 2.1Hz), 6.30
(Br, 1H) IR (film): ν3422,3314,2958,2916,2880,2104,1736,1
460,1417,1373,1323,1265,1241,1166,1143,1071,1006,9
57,853,745,671,646,603cm- ¹ Example 7 0.404 g (1.40 mmol) of (13) is placed in a reaction vessel, and the inside is replaced with argon. A solution prepared by dissolving 0.34 g (2.78 mmol) of dimethylaminopyridine in anhydrous CH ₂ Cl ₂ was added by a cannula, and the mixture was stirred to dissolve (13), and the vessel was cooled with ice. Then, 1.95 ml (14.0 mmol) of triethylamine was added, and 0.54 ml (6.98 mmol) of methanesulfonyl chloride was added.
Was added dropwise and stirred at 0 ° C. The reaction was followed by TLC, and after 3 minutes, it was confirmed that (13) had disappeared. 10 ml of water was added to the reaction solution, the temperature was returned to room temperature, and the organic layer was washed and separated. The aqueous layer was extracted 3 times with CH ₂ Cl ₂ 15 ml, washed CH ₂ Cl ₂ layer with saturated brine, dried over anhydrous MgSO _4, and the solvent was removed to give the crude product. This is repeated twice by silica gel column chromatography (flash SiO ₂ 5 g, CH ₂ Cl ₂ → ethyl acetate; flash SiO ₂ 10 g, hexane / ethyl acetate = 9).
Purify 0.292 g (1.07 mmol) of (Ig) as a yellow oil.
l), obtained in a yield of 77%. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 0.66 (q, 6H, J = 8.0 Hz),
0.98 (t, 9H, J = 8.0Hz), 2.5-2.9 (m, 4H), 3.11 (s, 1
H), 4,50 (d, 2H, J = 8.0Hz), 5.65 (br, 1H), 6.57 (br, 1
H) IR (film): ν3298, 2958, 2916, 2878, 2214, 1620, 1460, 1
415,1369,1241,1168,1079,1006,835,745,646cm- ¹ Example 8 Put 223mg (0.82mmol) of (Ig) in the reaction vessel and put it there
0.41 ml of THF, 0.41 ml of water and 0.41 ml of acetic acid were added using a syringe, and the mixture was stirred at room temperature. Follow the reaction by TLC, and after 45 minutes (I
g) was confirmed to have disappeared. To the reaction solution was added 3 ml of a saturated aqueous solution of sodium hydrogen carbonate, and the mixture was stirred to separate an organic layer. The aqueous layer was extracted three times with 5 ml of ether, and the ether layer was combined with the previous organic layer, washed with saturated saline, and then dried.
After drying over MgSO ₄ , the solvent was removed to obtain a crude product. This is subjected to silica gel column chromatography (flash SiO ₂ 10
g, hexane / ethyl acetate = 3.5) to give 121 mg (0.76 mmol) of (Ih) as a pale yellow oil in 93% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 1.74 (br, 1 H), 2.5-2.9
(M, 4H), 3.13 (s, 1H), 4.44 (br.s, 2H), 5.66 (br, 1
H), 6.59 (br, 1H) IR (film): ν3292,2918,2868,2844,2212,2108,1850,1
618,1582,1441,1423,1361,1342,1317,1284,1228,1168,1
011,924,833,764,640,605,524,472cm- ¹ Example 9 120 mg (0.759 mmol) of (Ih) is placed in a reaction vessel, and the inside is replaced with argon. Here, anhydrous CH ₂ Cl ₂ is added,
(Ih) was melted, and the vessel was cooled with ice and stirred. Thereto was added 0.21 ml (1.51 mmol) of triethylamine, and 0.12 ml (1.55 mmol) of methanesulfonyl chloride was added dropwise.
After stirring at room temperature for 1 hour and then at room temperature for 2 nights, TLC confirmed that the reaction was completed. 5 ml of water was added to the reaction solution, and the organic layer was washed and separated. The aqueous layer was extracted three times with 8 ml of CH ₂ Cl ₂ ,
The H ₂ Cl ₂ layer was washed with saturated saline 15 ml, dried over anhydrous MgSO ₄ ,
The solvent was removed to obtain a crude product. This is repeated twice with silica gel column chromatography (flash SiO ₂ 10
g, hexane / ethyl acetate = 10; flash SiO ₂ 3 g, hexane / ethyl acetate = 10) to give 81 mg (0.460 mmol) of (Ii) as a red-brown oil in 61% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 2.5-2.9 (m, 4H), 3.12.
(S, 1H), 4.33 (d, 1H, J = 2.2Hz), 5.66 (br.s, 1H), 6.6
2 (br.t, 1H, J = 3.1 Hz) IR (film): ν3294,3028,2920,2844,2212,2110,1850,1
618,1582,1441,1342,1317,1261,1181,1141,1038,998,92
4,849,832,797,764,688,636,607,491,439cm- ¹ Example 10 48 mg (0.274 mmol) of (12) is placed in a reaction vessel, and the inside is replaced with argon. Here is dimethylaminopyridine
A solution prepared by dissolving 70 mg (0.573 mmol) in 2.7 ml of anhydrous CH ₂ Cl ₂ was added by a cannula, and the mixture was stirred to dissolve (12), and the vessel was cooled with ice. Then, 0.38 ml (2.73 mmol) of triethylamine is added, and 0.15 ml (1.94 mmol) of methanesulfonyl chloride is added.
Was added dropwise over about 1 minute and stirred at 0 ° C. After 30 minutes, the reaction vessel was returned to room temperature and further stirred. The reaction was followed by TLC, and it was confirmed that (12) had disappeared after 6 hours. 5 ml of water was added to the reaction solution, and the organic layer was washed and separated. The aqueous layer was extracted 3 times with CH ₂ Cl ₂ 7 ml, washed CH ₂ Cl ₂ layer with saturated brine, dried over anhydrous MgSO _4, and the solvent was removed to give the crude product of reddish brown. This was purified using silica gel column chromatography (flash SiO ₂ 10 g, hexane / ethyl acetate = 9) to give (Ii) as a yellow oil.
2 mg (0.125 mmol) were obtained in a yield of 45%.

The experiment was carried out in the same manner except that 10 equivalents of lithium chloride were added to the substrate. However, neither the reaction time nor the yield (6 hours, 49%) was substantially changed. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 2.5-2.9 (m, 4H), 3.12.
(S, 1H), 4.33 (d, 1H, J = 2.2Hz), 5.66 (br.s, 1H), 6.6
2 (br.t, 1H, J = 3.1 Hz) IR (film): ν3294,3028,2920,2844,2212,2110,1850,1
618,1582,1441,1342,1317,1261,1181,1141,1038,998,92
4,849,832,797,764,688,636,607,491,439cm ^-1 Reference Example 14 Under argon atmosphere (3) 5.007 g (24.9 mmol) in THF 25m
l dissolved in. Here, at room temperature, an EtMgBrTHF solution (1.
43.4M) was slowly added, followed by stirring. A slight exotherm occurred during the addition and gas was evolved. After the addition, the mixture was heated to 50 ° C., and returned to room temperature after 30 minutes. Acetaldehyde after 10 minutes
2.8 ml (50.1 mmol) of a 20 ml THF solution was added dropwise. The reaction was confirmed by TLC, and a saturated aqueous solution of NH ₄ Cl was added 80 minutes later. 40 ml of ether was added, the organic layer was separated, and the aqueous layer was extracted twice with 20 ml of ether. The organic layers were combined, washed with 100 ml of a saturated saline solution, and dried over anhydrous MgSO ₄ . After removing the solvent, the residue was purified by silica gel column chromatography (SiO ₂ 150 g, hexane / ethyl acetate = 2.5) to give a colorless oil (4).
3.5076 g (14.31 mmol) in a yield of 57%. At the same time, 1.926 g (38%) of the raw material (3) was recovered. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 1.43 (d, 1 H, J = 6.6 Hz),
1.90-2.50 (m, 6H, pentacyclic methylene and hydroxyl group), 2.50 (dd, 1
H, J = 2.0Hz, 16.5Hz), 2.65 (dd, 1H, J = 2.0Hz, 16.5Hz),
4.51 (br.tq, 1H, J = 2.0Hz, 6.6Hz), 6.06 (t, 1H, J = 2.5H
z) IR (film): ν3336,2980,2934,2856,1622,1427,1371,1
325,1158,1067,1004,965,940,893,843cm ^-1 Reference Example 15 A reaction vessel with _{CuI288mg (1.51mmol) Pd (PPh 3} ) 4 417mg
(0.361 mmol), and the inside was replaced with argon. Here, (4) 1.7760 g (7.245 mmol), n-butylamine 85
9μ (8.69mmol), TMS-acetylene 1.23ml (8.70mmo
l) dissolved in 15 ml of dry benzene was added at room temperature, 30 ml of dry benzene was further added, and the mixture was stirred as it was.
The progress of the reaction was confirmed by TLC. Since (4) had disappeared after 2 hours and 30 minutes, 20 ml of water was added to stop the reaction. The organic layer was separated and the aqueous layer was extracted twice with 10 ml of ether. The organic layers were combined, washed with a saturated saline solution, and dried over anhydrous MgSO ₄ . After removing the solvent, a brown tar-like crude product was obtained. This is purified by silica gel column chromatography (SiO ₂
35 g, CH ₂ Cl ₂ → hexane / ethyl acetate = 1; SiO ₂ 50 g, hexane / ethyl acetate = 2) to give brown oil (5) as 1.6897
g (6.439 mmol) in 89% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 0.21 (s, 9H), 1.44 (d, 3
H, J = 6.6 Hz), 1.80-2.50 (m, 6H, 5-membered methylene and hydroxyl group), 2.50 (dd, 1H, J = 2.0 Hz, 16.7 Hz), 2.74 (dd, 1H, J =
2.0Hz, 16.7Hz), 4.52 (m, 1H), 6.24 (t, 1H, J = 2.8Hz) IR (film): ν3374,3060,2964,2906,2852,2252,2148,1
452,1424,1408,1371,1321,1251,1158,1067,1004,959,92
8,888,845,760,700,663,640cm ^-1 Reference Example 16 Under argon atmosphere (5) 1.5888 g (6.0544 mmol) in THF
Dissolved in 12 ml. Here, a 1.0 M THF solution of tetrabutylammonium fluoride (TBAF) was added at room temperature to 6.4 m
l (6.4 mmol) was added dropwise and stirred. After the dropwise addition, the reaction solution changed from light brown to dark brown, and the raw material (5) disappeared in 4 minutes. The THF was evaporated as it was to obtain a brown tar-like crude product. This was purified by silica gel column chromatography (SiO ₄ 45 g, hexane / ethyl acetate = 1.5), and 1.0642 g (5.594 mmol) of red-orange oil (6) was obtained.
Obtained in 92% yield. ¹ H-NMR (90 MHz, CDCl ₃ ): δ 1.43 (d, 3H, J = 6.6 Hz),
1.72-2.53 (m, 6H, 5-membered methylene and hydroxyl group), 2.54 (d
d, 1H, J = 1.7Hz, 16.7Hz), 2.74 (dd, 1H, J = 1.7Hz, 16.7H
z), 3.06 (s, 1H), 4.51 (br.tq, 1H, J = 1.7Hz, 6,6Hz),
6.30 (t, 1H, J = 3.1Hz) IR (film): ν3368,3292,3058,2982,2936,2852,2252,2
102,1452,1425,1371,1325,1291,1236,1156,1067,1004,9
57,928,890,855,652cm- ¹ Example 11 Oxalic acid dichloride ((COC
l) ₂₎ dissolved 0.31ml a (3.55 mmol) in anhydrous CH ₂ Cl ₂ 10ml, previously cooled to -60 ° C.. Here is DMSO 0.42ml (5.92mm
The ol) what was dissolved in anhydrous CH ₂ Cl ₂ 5 ml was added dropwise over 8 minutes, followed by stirring. After the dropwise addition, the mixture was stirred at −60 ° C. for 10 minutes, and then a solution prepared by dissolving 134.9 mg (0.7091 mmol) of (6) in 5 ml of anhydrous CH ₂ Cl ₂ was dropped and stirred for 10 minutes. After the addition, the mixture was stirred for 20 minutes, during which the solution gradually became cloudy. Next, 1.64 ml (11.7 mmol) of triethylamine was added dropwise over 4 minutes, and the mixture was stirred for 15 minutes. At this time, the pale yellow solution gradually turned dark brown. After addition of 20 ml of water, the temperature was returned to room temperature, and the reaction mixture was extracted three times with 10 ml of CH ₂ Cl ₂ . After the organic layer is dried over anhydrous MgSO ₄ , the solvent is evaporated at a temperature of 30 ° C. or lower, and concentrated to about 1 ml. The resulting black solution was immediately flash column chromatographed (SiO ₂ 25
g, pentane / ether = 5).
The fraction (a) was obtained at a low temperature using a vacuum pump (−10
(About ℃). 61.1 mg of (Ia) as colorless needles
(0.359 mmol), 51% yield.

mp 75.5-77.5 ° C ¹ H-NMR (90 MHz, CDCl ₃ ): δ 2.38 (s, 3H), 2.49-2.7
6 (m, 2H), 2.76-2.96 (m, 2H), 3.18 (s, 1H), 5.75 (b
rs, 1H), 6.78 (t, 1H, J = 2.8Hz) IR (KBr): ν3224,2184,2170,1657,1607,1578,1437,13
59,1319,1290,1243,1207,1087,1025,994,963,924,866,8
30,764,725,692,605,576,545,487,451,418 cm ^-1 [Effect of the Invention] The compound (I) of the present invention is an intermediate for advantageously producing the above-mentioned NCS-C and bicyclo [8.3.0] trideca-9,13-diene-2,7-diyne derivative. Useful as a body.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical indication location C07C 49/21 8114-4H C07C 49/21 69/025 69/025 A C07F 7/08 C07F 7 / 08 A 7/18 7/18 A // C07H 17/04 C07H 17/04

Claims (1)

(57) [Claims] 1. The following general formula (I) [Wherein, R ¹ represents a hydrogen atom or an organic silyl group, and R ² represents a halogenomethyl group, a hydroxymethyl group, an organic silyloxymethyl group, an acyloxymethyl group, or an acyl group]. Ethynyl-2-cyclopentenylidene) -2-butyne derivatives.