3-methylcyclohex-2-en-1-one

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: First, 3-methyl-cyclohexenone was prepared in accordance with the procedures of Jirgensons et. al., Euro. J. Med. Chem. 35 (2000) 555-565. Then, 3-methyl-cyclohexenone was reacted with methyl magnesium iodide in the presence of cuprous chloride in diethyl ether to obtain the title compound.

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

実験手順: A mixture of 3-methyl-2-cyclohexenone (4 g, 36.36 mmol), toluenesulfonic acid (100 mg) and ethylene glycol (7 mL) in 100 mL of toluene is refluxed overnight and water formed is removed by Dean- Stark trap. The residue after concentration is chromatographed on silica gel (10% ethyl acetate/hexane) to give 3.36 g (62%) of 7-methyl-1,4-dioxa-spiro[4.5]dec-7-ene. is refluxed overnight is removed by Dean- Stark trap The residue after concentration is chromatographed on silica gel (10% ethyl acetate/hexane)

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 500 mL flame dried round-bottomed flask was added copper(I) iodide (18 g) in ether (200 mL) to give a suspension. After cooling to −5° C., methyllithium (120 mL, 1.6M in ether) was added dropwise. After stirring at −5° C. for 1 hour, 3-methylcyclohex-2-enone (5.15 mL) in 15 ml ether was added dropwise, and the mixture was stirred at −5° C. for 1 hour. After cooling to −78° C., hexamethylphosphoramide (60 mL) was added dropwise. Ethyl carbonocyanidate (23.74 mL) was added. After stirring at −78° C. for 20 minutes, the mixture was warmed up to room temperature, and stirred for 1 hour. The mixture was poured into cold water, and the layers were separated. The aqueous layer was extracted with ether (3×20 mL). The combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL), dried over Na2SO4, filtered, and dried under vacuum. The crude product was added to a silica gel column and purified by eluting with 0-10% ethyl acetate in hexane. Into a 500 mL flame dried round-bottomed flask to give a suspension the mixture was stirred at −5° C. for 1 hour After cooling to −78° C. After stirring at −78° C. for 20 minutes the mixture was warmed up to room temperature stirred for 1 hour the layers were separated The aqueous layer was extracted with ether (3×20 mL) The combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL) dried over Na2SO4 filtered dried under vacuum The crude product was added to a silica gel column purified by eluting with 0-10% ethyl acetate in hexane

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

実験手順: A mixture of 3-methyl-2-cyclohexenone (4 g, 36.36 mmol), toluenesulfonic acid (100 mg) and ethylene glycol (7 mL) in 100 mL of toluene is refluxed overnight and water formed is removed by Dean-Stark trap. The residue after concentration is chromatographed on silica gel (10% ethyl acetate/hexane) to give 3.36 g (62%) of 7-methyl-1,4-dioxa-spiro[4.5]dec-7-ene. is refluxed overnight is removed by Dean-Stark trap The residue after concentration is chromatographed on silica gel (10% ethyl acetate/hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Freshly distilled azidotrimethylsilane (2.65 mL, 20 mmol) was added to a stirred solution of 3-methyl-2-cyclohexen-1-one (Compound 1, 1.13 mL, 10 mmol) and dichloromethane (15 mL) at 0° C. under argon. The solution was stirred for 2 hours at 0° C. before adding a solution of iodine (5.08 g, 20 mmol) in 15 mL of pyridine and 15 mL of dichloromethane. The resulting solution was stirred for 4 hours at room temperature, diluted with ethyl acetate, and was washed successively with 20% aqueous Na2S2O3, 10% aqueous HCl, water, and brine. The solvents were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (7:1, hexanes: ethyl acetate) to give the title compound as a yellow oil. The resulting solution was stirred for 4 hours at room temperature was washed successively with 20% aqueous Na2S2O3, 10% aqueous HCl, water, and brine The solvents were dried (MgSO4) concentrated under reduced pressure The residue was purified by flash chromatography on silica gel (7:1, hexanes: ethyl acetate)

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ozone was passed through a solution of 2.0 gms of 3-methyl-2-cyclohexenone at -78° C. for 30 minutes. The mixture was warmed to -20° C. and treated with a solution of 3.0 g of 30% hydrogen peroxide in 3.0 g of 50% NaOH. A drop of Adogen 464 was added and the two phase mixture was stirred vigorously for 1 hour. The aqueous phase was separated and acidified then extracted with ether. Removal of the ether afforded 1.12 g (48%) of 5-keto-hexanoic acid. The identity of the acid was confirmed by comparing the IR spectra of its methyl ester to the known spectra of the same compound. The aqueous phase was separated acidified then extracted with ether Removal of the ether

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ozone was passed through a solution of 2.0 gms of 3-methyl-2-cyclohexenone at -78° C. for 30 minutes. The mixture was warmed to -20° C. and treated with a solution of 3.0 g of 30% hydrogen peroxide in 3.0 g of 50% NaOH. A drop of Adogen 464 was added and the two phase mixture was stirred vigorously for 1 hour. The aqueous phase was separated and acidified then extracted with ether. Removal of the ether afforded 1.12 g (48%) of 5-keto-hexanoic acid. The identity of the acid was confirmed by comparing the IR spectra of its methyl ester to the known spectra of the same compound. The aqueous phase was separated acidified then extracted with ether Removal of the ether

反応条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (1R,2R)-1,2-diphenyl-1,2-ethanediol (150 g, 699 mmol) and 3-methyl-2-cyclohexen-1-one (77 g, 699 mmol) were suspended in benzene (1398 mL) and treated with PPTS (4.39 g, 17.48 mmol). The flask was fitted with a Dean-Stark trap filled with benzene and a condenser. The reaction was heated to 115° C. for 3 days, and then the reaction was cooled to ambient temperature and diluted with ether. The mixture was washed with saturated aq NaHCO3. The organic layer was dried over MgSO4, filtered and concentrated to give a red/orange liquid (214 g, 100% yield). The liquid was used without further purification. The flask was fitted with a Dean-Stark trap the reaction was cooled to ambient temperature The mixture was washed with saturated aq NaHCO3 The organic layer was dried over MgSO4 filtered concentrated

反応条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (1R,2R)-1,2-diphenyl-1,2-ethanediol (150 g, 699 mmol) and 3-methyl-2-cyclohexen-1-one (77 g, 699 mmol) were suspended in benzene (1398 mL) and treated with PPTS (4.39 g, 17.48 mmol). The flask was fitted with a Dean-Stark trap filled with benzene and a condenser. The reaction was heated to 115° C. for 3 days, and then the reaction was cooled to ambient temperature and diluted with ether. The mixture was washed with saturated aq NaHCO3. The organic layer was dried over MgSO4, filtered and concentrated to give a red/orange liquid (214 g, 100% yield). The liquid was used without further purification. The flask was fitted with a Dean-Stark trap the reaction was cooled to ambient temperature The mixture was washed with saturated aq NaHCO3 The organic layer was dried over MgSO4 filtered concentrated

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 500 mL flame dried round-bottomed flask was added copper(I) iodide (18 g) in ether (200 mL) to give a suspension. After cooling to −5° C., methyllithium (120 mL, 1.6M in ether) was added dropwise. After stirring at −5° C. for 1 hour, 3-methylcyclohex-2-enone (5.15 mL) in 15 ml ether was added dropwise, and the mixture was stirred at −5° C. for 1 hour. After cooling to −78° C., hexamethylphosphoramide (60 mL) was added dropwise. Ethyl carbonocyanidate (23.74 mL) was added. After stirring at −78° C. for 20 minutes, the mixture was warmed up to room temperature, and stirred for 1 hour. The mixture was poured into cold water, and the layers were separated. The aqueous layer was extracted with ether (3×20 mL). The combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL), dried over Na2SO4, filtered, and dried under vacuum. The crude product was added to a silica gel column and purified by eluting with 0-10% ethyl acetate in hexane. Into a 500 mL flame dried round-bottomed flask to give a suspension the mixture was stirred at −5° C. for 1 hour After cooling to −78° C. After stirring at −78° C. for 20 minutes the mixture was warmed up to room temperature stirred for 1 hour the layers were separated The aqueous layer was extracted with ether (3×20 mL) The combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL) dried over Na2SO4 filtered dried under vacuum The crude product was added to a silica gel column purified by eluting with 0-10% ethyl acetate in hexane

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 500 mL flame dried round-bottomed flask was added copper(I) iodide (18 g) in ether (200 mL) to give a suspension. After cooling to −5° C., methyllithium (120 mL, 1.6M in ether) was added dropwise. After stirring at −5° C. for 1 hour, 3-methylcyclohex-2-enone (5.15 mL) in 15 ml ether was added dropwise, and the mixture was stirred at −5° C. for 1 hour. After cooling to 78° C., hexamethylphosphoramide (60 mL) was added dropwise. Ethyl carbonocyanidate (23.74 mL) was added. After stirring at −78° C. for 20 minutes, the mixture was warmed up to room temperature, and stirred for 1 hour. The mixture was poured into cold water, and the layers were separated. The aqueous layer was extracted with ether (3×20 mL). The combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL), dried over Na2SO4, filtered, and dried under vacuum. The crude product was added to a silica gel column and purified by eluting with 0-10% ethyl acetate in hexane. Into a 500 mL flame dried round-bottomed flask to give a suspension the mixture was stirred at −5° C. for 1 hour After cooling to 78° C. After stirring at −78° C. for 20 minutes the mixture was warmed up to room temperature stirred for 1 hour the layers were separated The aqueous layer was extracted with ether (3×20 mL) The combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL) dried over Na2SO4 filtered dried under vacuum The crude product was added to a silica gel column purified by eluting with 0-10% ethyl acetate in hexane