3-(环己氧基)丙-1-醇

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 10 parts of 3-(cyclohexyloxy)-1-propanol in 160 parts of dichloromethane there were added 11.2 parts of N,N-diethylethanamine and dropwise 8.14 parts of methanesulfonyl chloride. The whole was stirred for 9 hours at room temperature. The reaction mixture was washed with Na2CO3 (aq.) and water and was then dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 99:1). The eluent of the desired fraction was evaporated and the residue was co-evaporated with methylbenzene. The product was filtered off and dried, yielding 8.6 parts (57.8%) of 3-(cyclohexyloxy)-1-propanol methanesulfonate (ester) (interm. 21). The reaction mixture was washed with Na2CO3 (aq.) and water was then dried filtered evaporated The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 99:1) The eluent of the desired fraction was evaporated The product was filtered off dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 10 parts of 3-(cyclohexyloxy)-1-propanol in 160 parts of dichloromethane there were added 11.2 parts of N,N-diethylethanamine and dropwise 8.14 parts of methanesulfonyl chloride. The whole was stirred for 9 hours at room temperature. The reaction mixture was washed with Na2CO3 (aq.) and water and was then dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 99:1). The eluent of the desired fraction was evaporated and the residue was co-evaporated with methylbenzene. The product was filtered off and dried, yielding 8.6 parts (57.8%) of 3-(cyclohexyloxy)-1-propanol methanesulfonate (ester) (interm. 21). The reaction mixture was washed with Na2CO3 (aq.) and water was then dried filtered evaporated The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 99:1) The eluent of the desired fraction was evaporated The product was filtered off dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The obtained 3-cyclohexyloxypropan-1-ol (11.5 g, 72.9 mmol) was dissolved in dichloromethane (240 ml), and then molecular sieve 4 Å (58 g) and pyridinium chlorochromate (23.8 g, 0.11 mol) were added thereto in the ice bath followed by stirring under a nitrogen atmosphere for 1 hour and 40 minutes. The reaction solution was diluted with ether, and then the solution was filtered through Celite. The Celite was washed with diethyl ether, and this filtrate was added to the previous filtrate. The total filtrate was evaporated in vacuo, and the residue was purified roughly by chromatography on a silica gel column (elution solvent; n-hexane:ethyl acetate=20:1-10:1) to give a crude 3-cyclohexyloxypropionaldehyde (8.6 g). the solution was filtered through Celite The Celite was washed with diethyl ether this filtrate was added to the previous filtrate The total filtrate was evaporated in vacuo the residue was purified roughly by chromatography on a silica gel column (elution solvent; n-hexane:ethyl acetate=20:1-10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-(Cyclohexyloxy)propan-1-ol (820 mg) synthesized in Reference Example 47 was dissolved in dichloromethane (20 mL), triethylamine (1.1 mL), p-toluenesulfonyl chloride (1.2 g) and 4-dimethylaminopyridine (63 mg) were added thereto, and the mixture was stirred at room temperature overnight. Water was added to the reaction solution, and the organic layer was separated and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=5:1) to give the title compound (1.0 g) as a colorless oil. the organic layer was separated dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=5:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 10 parts of 3-(cyclohexyloxy)-1-propanol in 160 parts of dichloromethane there were added 11.2 parts of N,N-diethylethanamine and dropwise 8.14 parts of methanesulfonyl chloride. The whole was stirred for 9 hours at room temperature. The reaction mixture was washed with Na2CO3 (aq.) and water and was then dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 99:1). The eluent of the desired fraction was evaporated and the residue was co-evaporated with methylbenzene. The product was filtered off and dried, yielding 8.6 parts (57.8%) of 3-(cyclohexyloxy)-1-propanol methanesulfonate (ester) (interm. 21). The reaction mixture was washed with Na2CO3 (aq.) and water was then dried filtered evaporated The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 99:1) The eluent of the desired fraction was evaporated The product was filtered off dried

反应条件: temp:0.00; pressure:0.00; stir: