nona-1,8-dien-5-ol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml-capacity three neck flask containing a stirring bar and connected to a condenser was sufficiently dried. Then, a nitrogen atmosphere was established in the flask, and 1,8-nonadiene-5-ol (8) (3.72 g, 2.66 mmol), PPh3 (6.98 g, 2.66 mmol), and 4-nitrophenol (4.43 g, 3.19 mmol) were introduced into the flask. Dried THF (50 ml) was further added to the mixture, the mixture thus obtained was stirred at room temperature, DEAD (12.2 ml, 3.19 mmol) was then dropped into the flask, and the mixture thus obtained was stirred for 5 hours. When generation of ether was recognized by thin-layer chromatography (hexane:ethyl acetate=10:1), the solvent was distilled off under reduced pressure, the mixture was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1). Thus, 1-nitro-4-(1,8-nonadiene-5-yloxy)benzene (11) (4.731 g, 1.7 mmol, yield: 65%) was obtained as an intended compound. 1HNMR values of 1-nitro-4-(1,8-nonadiene-5-yloxy)benzene (11) are shown below. A 300 ml-capacity three neck flask containing a stirring bar connected to a condenser was sufficiently dried were introduced into the flask the mixture thus obtained the mixture thus obtained was stirred for 5 hours the solvent was distilled off under reduced pressure the mixture was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml-capacity three neck flask containing a stirring bar and connected to a condenser was sufficiently dried. Then, a nitrogen atmosphere was established in the flask, and 1,8-nonadiene-5-ol (8) (3.72 g, 2.66 mmol), PPh3 (6.98 g, 2.66 mmol), and 4-nitrophenol (4.43 g, 3.19 mmol) were introduced into the flask. Dried THF (50 ml) was further added to the mixture, the mixture thus obtained was stirred at room temperature, DEAD (12.2 ml, 3.19 mmol) was then dropped into the flask, and the mixture thus obtained was stirred for 5 hours. When generation of ether was recognized by thin-layer chromatography (hexane:ethyl acetate=10:1), the solvent was distilled off under reduced pressure, the mixture was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1). Thus, 1-nitro-4-(1,8-nonadiene-5-yloxy)benzene (11) (4.731 g, 1.7 mmol, yield: 65%) was obtained as an intended compound. 1HNMR values of 1-nitro-4-(1,8-nonadiene-5-yloxy)benzene (11) are shown below. A 300 ml-capacity three neck flask containing a stirring bar connected to a condenser was sufficiently dried were introduced into the flask the mixture thus obtained the mixture thus obtained was stirred for 5 hours the solvent was distilled off under reduced pressure the mixture was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml-capacity three neck flask containing a stirring bar and Mg (8 g, 16.3 mmol) and connected to a condenser was sufficiently dried. Then, a nitrogen atmosphere was established in the flask, and diethyl ether (24.5 ml) and I2 were introduced into the flask. When a solution of 1-bromo-3-butene (7) (22 ml, 16.3 mmol) in diethyl ether (24.5 ml) was slowly added to the brown suspension thus obtained, a reaction started, and a color of I2 disappeared. After generation of a Grignard reagent, HCOOMe (9.78 ml, 16.3 mmol) was slowly dropped into the flask, and the mixture thus obtained was stirred for 30 minutes. Subsequently, when generation of alcohol was recognized by thin-layer chromatography (hexane:ethyl acetate=10:1), diluted hydrochloric acid was added to the mixture to stop the reaction. After cooling the mixture, an organic layer was separated and extracted with ethyl acetate. This organic layer was dehydrated over Na2SO4 and filtered. The solvent was distilled off, and the organic layer was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1). Thus, 1,8-nonadiene-5-ol (8) (11.613 g, 8.3 mmol, yield: 51%) was obtained as an intended compound. A 300 ml-capacity three neck flask containing a stirring bar was sufficiently dried were introduced into the flask thus obtained the mixture thus obtained was added to the mixture the reaction After cooling the mixture an organic layer was separated extracted with ethyl acetate filtered The solvent was distilled off the organic layer was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.21 g (35 mmol) of triphenylphosphine, 4.50 g (32 mmol) of 1,8-nonadiene-5-ol (8), and 6.03 g (41 mmol) of phthalimide were dissolved in 150 ml of tetrahydrofuran. This solution thus obtained was stirred for 30 minutes, and at room temperature, 15 ml (33 mmol) of diethyl azodicarboxylate (2.2 mol/l solution in toluene) was thereafter dropped in the solution, which was then stirred for 12 hours. Subsequently, hexane was added to the solution, and a precipitate was filtered off, and the filtrate thus obtained was dried over sodium sulfate. The solvent was distilled off, and the crude product thus obtained was purified by silica gel column chromatography (eluent: hexane:ethyl acetate of 5:1). The product thus obtained was dissolved in 50 ml of methanol, and 3 ml of hydrazine hydrate was added to the solution thus obtained, which was then refluxed for 1 hour. The reaction solution thus obtained was cooled, and a white precipitate was obtained by filtration and was washed with methanol. The filtrate thus obtained was concentrated, hexane was then added to the filtrate, and a white precipitate thus produced was obtained by re-filtration and was washed with hexane. Then, the solvent was distilled off from this filtrate. Thus, 2.58 g (18 mmol) of a slightly yellow liquid was obtained as an intended compound (9). A yield of the compound (9) was 57%. 1,8-nonadiene-5-ol (8) as a synthetic starting material can be synthesized in the same manner as in Reference Example 8 (synthesis of starting material for Example 13) described below, for example. Values obtained by instrumental analysis of the compound (9) are shown below. This solution thus obtained was then stirred for 12 hours a precipitate was filtered off the filtrate thus obtained was dried over sodium sulfate The solvent was distilled off the crude product thus obtained was purified by silica gel column chromatography (eluent: hexane:ethyl acetate of 5:1) The product thus obtained thus obtained which was then refluxed for 1 hour The reaction solution thus obtained was cooled a white precipitate was obtained by filtration was washed with methanol The filtrate thus obtained was concentrated hexane was then added to the filtrate a white precipitate thus produced was obtained by re-filtration was washed with hexane Then, the solvent was distilled off from this filtrate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.21 g (35 mmol) of triphenylphosphine, 4.50 g (32 mmol) of 1,8-nonadiene-5-ol (8), and 6.03 g (41 mmol) of phthalimide were dissolved in 150 ml of tetrahydrofuran. This solution thus obtained was stirred for 30 minutes, and at room temperature, 15 ml (33 mmol) of diethyl azodicarboxylate (2.2 mol/l solution in toluene) was thereafter dropped in the solution, which was then stirred for 12 hours. Subsequently, hexane was added to the solution, and a precipitate was filtered off, and the filtrate thus obtained was dried over sodium sulfate. The solvent was distilled off, and the crude product thus obtained was purified by silica gel column chromatography (eluent: hexane:ethyl acetate of 5:1). The product thus obtained was dissolved in 50 ml of methanol, and 3 ml of hydrazine hydrate was added to the solution thus obtained, which was then refluxed for 1 hour. The reaction solution thus obtained was cooled, and a white precipitate was obtained by filtration and was washed with methanol. The filtrate thus obtained was concentrated, hexane was then added to the filtrate, and a white precipitate thus produced was obtained by re-filtration and was washed with hexane. Then, the solvent was distilled off from this filtrate. Thus, 2.58 g (18 mmol) of a slightly yellow liquid was obtained as an intended compound (9). A yield of the compound (9) was 57%. 1,8-nonadiene-5-ol (8) as a synthetic starting material can be synthesized in the same manner as in Reference Example 8 (synthesis of starting material for Example 13) described below, for example. Values obtained by instrumental analysis of the compound (9) are shown below. This solution thus obtained was then stirred for 12 hours a precipitate was filtered off the filtrate thus obtained was dried over sodium sulfate The solvent was distilled off the crude product thus obtained was purified by silica gel column chromatography (eluent: hexane:ethyl acetate of 5:1) The product thus obtained thus obtained which was then refluxed for 1 hour The reaction solution thus obtained was cooled a white precipitate was obtained by filtration was washed with methanol The filtrate thus obtained was concentrated hexane was then added to the filtrate a white precipitate thus produced was obtained by re-filtration was washed with hexane Then, the solvent was distilled off from this filtrate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Butenyl-magnesium bromide (125 mL, 0.5 M in tetrahydrofuran, 62.5 mmol) was added drop wise to a stirred and cooled (−78° C.) solution of pent-4-enal (4 g, 48.07 mmol) in dry tetrahydrofuran (160 mL). After the addition, the solution was warmed to room temperature and then quenched with NH4Cl solution. The mixture was partitioned with diethyl ether and the organic phase was washed with brine, dried (MgSO4), filtered, and evaporated. The residue was purified over silica gel using 5-15% diethyl ether in hexanes to give the title compound as an oil. After the addition quenched with NH4Cl solution The mixture was partitioned with diethyl ether the organic phase was washed with brine dried (MgSO4) filtered evaporated The residue was purified over silica gel using 5-15% diethyl ether in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Butenyl-magnesium bromide (125 mL, 0.5 M in tetrahydrofuran, 62.5 mmol) was added drop wise to a stirred and cooled (−78° C.) solution of pent-4-enal (4 g, 48.07 mmol) in dry tetrahydrofuran (160 mL). After the addition, the solution was warmed to room temperature and then quenched with NH4Cl solution. The mixture was partitioned with diethyl ether and the organic phase was washed with brine, dried (MgSO4), filtered, and evaporated. The residue was purified over silica gel using 5-15% diethyl ether in hexanes to give the title compound as an oil. After the addition quenched with NH4Cl solution The mixture was partitioned with diethyl ether the organic phase was washed with brine dried (MgSO4) filtered evaporated The residue was purified over silica gel using 5-15% diethyl ether in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Butenyl-magnesium bromide (125 mL, 0.5 M in tetrahydrofuran, 62.5 mmol) was added drop wise to a stirred and cooled (−78° C.) solution of pent-4-enal (4 g, 48.07 mmol) in dry tetrahydrofuran (160 mL). After the addition, the solution was warmed to room temperature and then quenched with NH4Cl solution. The mixture was partitioned with diethyl ether and the organic phase was washed with brine, dried (MgSO4), filtered, and evaporated. The residue was purified over silica gel using 5-15% diethyl ether in hexanes to give the title compound as an oil. After the addition quenched with NH4Cl solution The mixture was partitioned with diethyl ether the organic phase was washed with brine dried (MgSO4) filtered evaporated The residue was purified over silica gel using 5-15% diethyl ether in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.1 g of 60% sodium hydride was suspended in 50 ml of THF, and 6.6 g of 1,8-nonadien-5-ol was dropped therein in an atmosphere of argon. 28 g of 1,10-dibromodecane was further dropped therein, and reflux was then carried out for 21 hours in an atmosphere of argon. After the generated precipitate was filtered off, the solvent was evaporated, and the residue was purified by silica gel column chromatography, to obtain 5.3 g of the compound (7). (Yield: 31%) reflux After the generated precipitate was filtered off the solvent was evaporated the residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml-capacity three neck flask containing a stirring bar and connected to a condenser was sufficiently dried. Then, a nitrogen atmosphere was established in the flask, and 1,8-nonadiene-5-ol (8) (3.72 g, 2.66 mmol), PPh3 (6.98 g, 2.66 mmol), and 4-nitrophenol (4.43 g, 3.19 mmol) were introduced into the flask. Dried THF (50 ml) was further added to the mixture, the mixture thus obtained was stirred at room temperature, DEAD (12.2 ml, 3.19 mmol) was then dropped into the flask, and the mixture thus obtained was stirred for 5 hours. When generation of ether was recognized by thin-layer chromatography (hexane:ethyl acetate=10:1), the solvent was distilled off under reduced pressure, the mixture was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1). Thus, 1-nitro-4-(1,8-nonadiene-5-yloxy)benzene (11) (4.731 g, 1.7 mmol, yield: 65%) was obtained as an intended compound. 1HNMR values of 1-nitro-4-(1,8-nonadiene-5-yloxy)benzene (11) are shown below. A 300 ml-capacity three neck flask containing a stirring bar connected to a condenser was sufficiently dried were introduced into the flask the mixture thus obtained the mixture thus obtained was stirred for 5 hours the solvent was distilled off under reduced pressure the mixture was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml-capacity three neck flask containing a stirring bar and Mg (8 g, 16.3 mmol) and connected to a condenser was sufficiently dried. Then, a nitrogen atmosphere was established in the flask, and diethyl ether (24.5 ml) and I2 were introduced into the flask. When a solution of 1-bromo-3-butene (7) (22 ml, 16.3 mmol) in diethyl ether (24.5 ml) was slowly added to the brown suspension thus obtained, a reaction started, and a color of I2 disappeared. After generation of a Grignard reagent, HCOOMe (9.78 ml, 16.3 mmol) was slowly dropped into the flask, and the mixture thus obtained was stirred for 30 minutes. Subsequently, when generation of alcohol was recognized by thin-layer chromatography (hexane:ethyl acetate=10:1), diluted hydrochloric acid was added to the mixture to stop the reaction. After cooling the mixture, an organic layer was separated and extracted with ethyl acetate. This organic layer was dehydrated over Na2SO4 and filtered. The solvent was distilled off, and the organic layer was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1). Thus, 1,8-nonadiene-5-ol (8) (11.613 g, 8.3 mmol, yield: 51%) was obtained as an intended compound. A 300 ml-capacity three neck flask containing a stirring bar was sufficiently dried were introduced into the flask thus obtained the mixture thus obtained was added to the mixture the reaction After cooling the mixture an organic layer was separated extracted with ethyl acetate filtered The solvent was distilled off the organic layer was purified by flash chromatography on silica gel (hexane:ethyl acetate=10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.21 g (35 mmol) of triphenylphosphine, 4.50 g (32 mmol) of 1,8-nonadiene-5-ol (8), and 6.03 g (41 mmol) of phthalimide were dissolved in 150 ml of tetrahydrofuran. This solution thus obtained was stirred for 30 minutes, and at room temperature, 15 ml (33 mmol) of diethyl azodicarboxylate (2.2 mol/l solution in toluene) was thereafter dropped in the solution, which was then stirred for 12 hours. Subsequently, hexane was added to the solution, and a precipitate was filtered off, and the filtrate thus obtained was dried over sodium sulfate. The solvent was distilled off, and the crude product thus obtained was purified by silica gel column chromatography (eluent: hexane:ethyl acetate of 5:1). The product thus obtained was dissolved in 50 ml of methanol, and 3 ml of hydrazine hydrate was added to the solution thus obtained, which was then refluxed for 1 hour. The reaction solution thus obtained was cooled, and a white precipitate was obtained by filtration and was washed with methanol. The filtrate thus obtained was concentrated, hexane was then added to the filtrate, and a white precipitate thus produced was obtained by re-filtration and was washed with hexane. Then, the solvent was distilled off from this filtrate. Thus, 2.58 g (18 mmol) of a slightly yellow liquid was obtained as an intended compound (9). A yield of the compound (9) was 57%. 1,8-nonadiene-5-ol (8) as a synthetic starting material can be synthesized in the same manner as in Reference Example 8 (synthesis of starting material for Example 13) described below, for example. Values obtained by instrumental analysis of the compound (9) are shown below. This solution thus obtained was then stirred for 12 hours a precipitate was filtered off the filtrate thus obtained was dried over sodium sulfate The solvent was distilled off the crude product thus obtained was purified by silica gel column chromatography (eluent: hexane:ethyl acetate of 5:1) The product thus obtained thus obtained which was then refluxed for 1 hour The reaction solution thus obtained was cooled a white precipitate was obtained by filtration was washed with methanol The filtrate thus obtained was concentrated hexane was then added to the filtrate a white precipitate thus produced was obtained by re-filtration was washed with hexane Then, the solvent was distilled off from this filtrate