1,5-dioxaspiro[5.5]undecane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Subsequently, to a suspension of zirconium chloride (24.9 g, 0.11 mol) in tetrahydrofuran (500 ml) was added slowly sodium borohydride (20.5 g, 0.54 mol) in portions with stirring under a nitrogen atmosphere, and the resulting mixture was stirred at room temperature for 20 minutes. After stirring, to the reaction mixture was added dropwise a solution of cyclohexanone trimethylene ketal (16.9 g, 0.11 mol) obtained above in tetrahydrofuran (170 ml) with stirring while ice-cooling under a nitrogen atmosphere, and then the resulting mixture was stirred at room temperature for one day. After stirring, to the reaction mixture was added ice-chilled 2N hydrochloric acid (600 ml) with stirring under ice-cooling to quench the reaction, and then the tetrahydrofuran was evaporated in vacuo. The aqueous layer which remained was extracted with ethyl acetate, and the extract was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (10:1-5:2) as the eluent to afford 3-cyclohexyloxypropan-1-ol (13.4 g, yield: 78%). the resulting mixture was stirred at room temperature for 20 minutes After stirring, to the reaction mixture with stirring while ice- cooling under a nitrogen atmosphere the resulting mixture was stirred at room temperature for one day After stirring, to the reaction mixture was added ice- with stirring under ice- cooling to quench the reaction the tetrahydrofuran was evaporated in vacuo The aqueous layer which remained was extracted with ethyl acetate the extract was washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate After filtration the solvent was removed in vacuo the residue was purified by chromatography on a silica gel column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of cyclohexanone (32 ml, 0.31 mol) in dry dichloromethane (950 ml) were added successively 1,3-propanediol (33.5 ml, 0.46 mol), triethyl orthoformate (51.5 ml, 0.31 mol) and zirconium chloride (1.44 g, 6.18 mmol) with stirring, and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After stirring, ice-chilled 1N aqueous sodium hydroxide solution (1.5 l) was added to the reaction mixture with stirring, and the resulting mixture was extracted with dichloromethane. The extract was washed with water and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by reduced-pressure distillation to afford cyclohexanone trimethylene ketal (26.8 g, yield: 55%). the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour After stirring was added to the reaction mixture with stirring the resulting mixture was extracted with dichloromethane The extract was washed with water dried over anhydrous sodium sulfate After filtration the solvent was removed in vacuo the residue was purified by reduced-pressure distillation

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 14.0 ml (14.0 mmol) of a 1M hexane solution of diisobutylaluminum hydride were added dropwise over a period of 5 minutes to a solution of 1.01 g (647 mmol) of 1,5-dioxaspiro[5.5]-undecane in 5 ml of methylene chloride, and the resulting mixture was stirred for 1 hour at room temperature. At the end of this time, the reaction mixture was ice-cooled and 20 ml of methanol were added dropwise over a period of 5 minutes in order to stop the reaction. The mixture was stirred for 20 minutes at room temperature, and then 2N aqueous hydrochloric acid was added to dissolve the precipitate. The mixture was then extracted with diethyl ether. The extract was washed with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order. The organic phase was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through 25 g of silica gel, using a 3:1 by volume mixture of diethyl ether and hexane as the eluent, to give 774 mg (yield 76%) of the title alcohol derivative as an oil. cooled the reaction The mixture was stirred for 20 minutes at room temperature to dissolve the precipitate The mixture was then extracted with diethyl ether The extract was washed with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order The organic phase was dried over anhydrous magnesium sulfate the solvent was removed by distillation under reduced pressure The resulting residue was purified by column chromatography through 25 g of silica gel by volume mixture of diethyl ether and hexane as the eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 14.0 ml (14.0 mmol) of a 1M hexane solution of diisobutylaluminum hydride were added dropwise over a period of 5 minutes to a solution of 1.01 g (647 mmol) of 1,5-dioxaspiro[5.5]-undecane in 5 ml of methylene chloride, and the resulting mixture was stirred for 1 hour at room temperature. At the end of this time, the reaction mixture was ice-cooled and 20 ml of methanol were added dropwise over a period of 5 minutes in order to stop the reaction. The mixture was stirred for 20 minutes at room temperature, and then 2N aqueous hydrochloric acid was added to dissolve the precipitate. The mixture was then extracted with diethyl ether. The extract was washed with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order. The organic phase was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through 25 g of silica gel, using a 3:1 by volume mixture of diethyl ether and hexane as the eluent, to give 774 mg (yield 76%) of the title alcohol derivative as an oil. cooled the reaction The mixture was stirred for 20 minutes at room temperature to dissolve the precipitate The mixture was then extracted with diethyl ether The extract was washed with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order The organic phase was dried over anhydrous magnesium sulfate the solvent was removed by distillation under reduced pressure The resulting residue was purified by column chromatography through 25 g of silica gel by volume mixture of diethyl ether and hexane as the eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cyclohexanone (7.94 g) was dissolved in toluene (200 mL), 1,3-propanediol (12.3 g) and p-toluenesulfonic acid monohydrate (0.1 g) were added thereto, and the mixture was heated under reflux for 1.5 hr while removing water being produced. The temperature was allowed to cool to room temperature, and the mixture was washed with saturated aqueous sodium hydrogen carbonate solution and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (12.4 g) as a colorless oil. the mixture was heated under reflux for 1.5 hr while removing water being produced the mixture was washed with saturated aqueous sodium hydrogen carbonate solution dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Subsequently, to a suspension of zirconium chloride (24.9 g, 0.11 mol) in tetrahydrofuran (500 ml) was added slowly sodium borohydride (20.5 g, 0.54 mol) in portions with stirring under a nitrogen atmosphere, and the resulting mixture was stirred at room temperature for 20 minutes. After stirring, to the reaction mixture was added dropwise a solution of cyclohexanone trimethylene ketal (16.9 g, 0.11 mol) obtained above in tetrahydrofuran (170 ml) with stirring while ice-cooling under a nitrogen atmosphere, and then the resulting mixture was stirred at room temperature for one day. After stirring, to the reaction mixture was added ice-chilled 2N hydrochloric acid (600 ml) with stirring under ice-cooling to quench the reaction, and then the tetrahydrofuran was evaporated in vacuo. The aqueous layer which remained was extracted with ethyl acetate, and the extract was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (10:1-5:2) as the eluent to afford 3-cyclohexyloxypropan-1-ol (13.4 g, yield: 78%). the resulting mixture was stirred at room temperature for 20 minutes After stirring, to the reaction mixture with stirring while ice- cooling under a nitrogen atmosphere the resulting mixture was stirred at room temperature for one day After stirring, to the reaction mixture was added ice- with stirring under ice- cooling to quench the reaction the tetrahydrofuran was evaporated in vacuo The aqueous layer which remained was extracted with ethyl acetate the extract was washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate After filtration the solvent was removed in vacuo the residue was purified by chromatography on a silica gel column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of cyclohexanone (32 ml, 0.31 mol) in dry dichloromethane (950 ml) were added successively 1,3-propanediol (33.5 ml, 0.46 mol), triethyl orthoformate (51.5 ml, 0.31 mol) and zirconium chloride (1.44 g, 6.18 mmol) with stirring, and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After stirring, ice-chilled 1N aqueous sodium hydroxide solution (1.5 l) was added to the reaction mixture with stirring, and the resulting mixture was extracted with dichloromethane. The extract was washed with water and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by reduced-pressure distillation to afford cyclohexanone trimethylene ketal (26.8 g, yield: 55%). the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour After stirring was added to the reaction mixture with stirring the resulting mixture was extracted with dichloromethane The extract was washed with water dried over anhydrous sodium sulfate After filtration the solvent was removed in vacuo the residue was purified by reduced-pressure distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Subsequently, to a suspension of zirconium chloride (24.9 g, 0.11 mol) in tetrahydrofuran (500 ml) was added slowly sodium borohydride (20.5 g, 0.54 mol) in portions with stirring under a nitrogen atmosphere, and the resulting mixture was stirred at room temperature for 20 minutes. After stirring, to the reaction mixture was added dropwise a solution of cyclohexanone trimethylene ketal (16.9 g, 0.11 mol) obtained above in tetrahydrofuran (170 ml) with stirring while ice-cooling under a nitrogen atmosphere, and then the resulting mixture was stirred at room temperature for one day. After stirring, to the reaction mixture was added ice-chilled 2N hydrochloric acid (600 ml) with stirring under ice-cooling to quench the reaction, and then the tetrahydrofuran was evaporated in vacuo. The aqueous layer which remained was extracted with ethyl acetate, and the extract was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (10:1-5:2) as the eluent to afford 3-cyclohexyloxypropan-1-ol (13.4 g, yield: 78%). the resulting mixture was stirred at room temperature for 20 minutes After stirring, to the reaction mixture with stirring while ice- cooling under a nitrogen atmosphere the resulting mixture was stirred at room temperature for one day After stirring, to the reaction mixture was added ice- with stirring under ice- cooling to quench the reaction the tetrahydrofuran was evaporated in vacuo The aqueous layer which remained was extracted with ethyl acetate the extract was washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate After filtration the solvent was removed in vacuo the residue was purified by chromatography on a silica gel column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of cyclohexanone (32 ml, 0.31 mol) in dry dichloromethane (950 ml) were added successively 1,3-propanediol (33.5 ml, 0.46 mol), triethyl orthoformate (51.5 ml, 0.31 mol) and zirconium chloride (1.44 g, 6.18 mmol) with stirring, and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After stirring, ice-chilled 1N aqueous sodium hydroxide solution (1.5 l) was added to the reaction mixture with stirring, and the resulting mixture was extracted with dichloromethane. The extract was washed with water and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by reduced-pressure distillation to afford cyclohexanone trimethylene ketal (26.8 g, yield: 55%). the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour After stirring was added to the reaction mixture with stirring the resulting mixture was extracted with dichloromethane The extract was washed with water dried over anhydrous sodium sulfate After filtration the solvent was removed in vacuo the residue was purified by reduced-pressure distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of cyclohexanone (32 ml, 0.31 mol) in dry dichloromethane (950 ml) were added successively 1,3-propanediol (33.5 ml, 0.46 mol), triethyl orthoformate (51.5 ml, 0.31 mol) and zirconium chloride (1.44 g, 6.18 mmol) with stirring, and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After stirring, ice-chilled 1N aqueous sodium hydroxide solution (1.5 l) was added to the reaction mixture with stirring, and the resulting mixture was extracted with dichloromethane. The extract was washed with water and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by reduced-pressure distillation to afford cyclohexanone trimethylene ketal (26.8 g, yield: 55%). the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour After stirring was added to the reaction mixture with stirring the resulting mixture was extracted with dichloromethane The extract was washed with water dried over anhydrous sodium sulfate After filtration the solvent was removed in vacuo the residue was purified by reduced-pressure distillation