ethyl 2-(2-oxocyclohexyl)acetate

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: Under an argon atmosphere, ethylene glycol (7.6 ml, 135.87 mmol) and para-toluenesulfonic acid (516 mg, 2.72 mmol) were added to a solution of (±)-2-(ethoxycarbonylmethyl)cyclohexanone (5.00 g, 27.17 mmol) in toluene (136 ml). The mixture was heated to reflux in a Dean Stark apparatus for 4 h and then allowed to cool to room temperature and quenched with sodium bicarbonate (5 g) and a saturated sodium bicarbonate solution (150 ml). The organic phase was separated from the aqueous phase which was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with a saturated sodium bicarbonate solution (100 ml) and brine (100 ml). The organic phase was dried over magnesium sulphate and the solvent was evaporated under reduced pressure to give the crude product which was purified using flash column chromatography with hexane-ethyl acetate (9:1) to give (±)-6-(ethoxycarbonylmethyl)-1,4-dioxaspiro[4.5]decane (4.59 g, 74% yield) as a colourless oil. Rf 0.18 (hexane-ethyl acetate, 9:1). The mixture was heated to reflux in a Dean Stark apparatus for 4 h quenched with sodium bicarbonate (5 g) The organic phase was separated from the aqueous phase which was extracted with ethyl acetate (3×100 ml) The combined organic phases were washed with a saturated sodium bicarbonate solution (100 ml) and brine (100 ml) The organic phase was dried over magnesium sulphate the solvent was evaporated under reduced pressure to give the crude product which was purified

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

実験手順: 8.0 Parts of 4-chloro-2-fluorophenylhydrazine and 9.2 parts of ethyl 2-cyclohexanoneacetate [bp 92°-93°, 0.5 mm Hg; prepared by the method described by A. Sergre, et al., J. Amer. Chem. Soc., 79 3503 (1957)] were dissolved in 75 parts of glacial acetic acid, and the resulting solution was refluxed for 16 hours. The reaction solvent was removed under a reduced pressure of 300 mm Hg, and the residual brown oil was dissolved in 150 parts of methylene chloride. The organic solution was washed with saturated aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate and the solvent was removed under a reduced pressure of 300 mm Hg to give 2-(4-chloro-2-fluorophenyl)-4,4a,5,6,7,8-hexahydro-3(2H)-cinnolinone as a brown oil that solidified on scratching. Purification was achieved by recrystallization from cyclohexane to yield 5.9 parts of tan solid, mp 110°-112°. prepared by the method the resulting solution was refluxed for 16 hours The reaction solvent was removed under a reduced pressure of 300 mm Hg the residual brown oil was dissolved in 150 parts of methylene chloride The organic solution was washed with saturated aqueous sodium bicarbonate solution dried with anhydrous magnesium sulfate the solvent was removed under a reduced pressure of 300 mm Hg

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

実験手順: 8.0 Parts of 4-chloro-2-fluorophenylhydrazine and 9.2 parts of ethyl 2-cyclohexanoneacetate [bp 92°-93°, 0.5 mm Hg; prepared by the method described by A. Sergre, et al., J. Amer. Chem. Soc., 79 3503 (1957)] were dissolved in 75 parts of glacial acetic acid, and the resulting solution was refluxed for 16 hours. The reaction solvent was removed under a reduced pressure of 300 mm Hg, and the residual brown oil was dissolved in 150 parts of methylene chloride. The organic solution was washed with saturated aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate and the solvent was removed under a reduced pressure of 300 mm Hg to give 2-(4-chloro-2-fluorophenyl)-4,4a,5,6,7,8-hexahydro-3(2H)-cinnolinone as a brown oil that solidified on scratching. Purification was achieved by recrystallization from cyclohexane to yield 5.9 parts of tan solid, mp 110°-112°. prepared by the method the resulting solution was refluxed for 16 hours The reaction solvent was removed under a reduced pressure of 300 mm Hg the residual brown oil was dissolved in 150 parts of methylene chloride The organic solution was washed with saturated aqueous sodium bicarbonate solution dried with anhydrous magnesium sulfate the solvent was removed under a reduced pressure of 300 mm Hg

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

実験手順: Ethyl 2-cyclohexanoneacetate (4.28 g, 23.3 mmol) and O-benzyl hydroxylamine hydrochloride were combined in 100 mL of ethanol (EtOH) and 2.59 g (25.6 mmol, 3.55 mL) of triethyl amine(Et3N) was added. The reaction was stirred at room temperature for 12 hours at which point it was concentrated in vacuo. The residue was taken up in EtOAc and washed with 1N HCl (2×20 mL), saturated NaHCO3 (1×20 mL), dried over Na2SO4, filtered, and concentrated. Purification by chromatography (SiO2, 90:1 hexanes-EtOAc) afforded (2-benzyloxyimino-cyclohexyl)-acetic acid ethyl ester (4.76 g, 72%) as a mixture of oxime isomers. was concentrated in vacuo washed with 1N HCl (2×20 mL), saturated NaHCO3 (1×20 mL) dried over Na2SO4 filtered concentrated Purification by chromatography (SiO2, 90:1 hexanes-EtOAc)

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

実験手順: Under an argon atmosphere, ethylene glycol (7.6 ml, 135.87 mmol) and para-toluenesulfonic acid (516 mg, 2.72 mmol) were added to a solution of (±)-2-(ethoxycarbonylmethyl)cyclohexanone (5.00 g, 27.17 mmol) in toluene (136 ml). The mixture was heated to reflux in a Dean Stark apparatus for 4 h and then allowed to cool to room temperature and quenched with sodium bicarbonate (5 g) and a saturated sodium bicarbonate solution (150 ml). The organic phase was separated from the aqueous phase which was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with a saturated sodium bicarbonate solution (100 ml) and brine (100 ml). The organic phase was dried over magnesium sulphate and the solvent was evaporated under reduced pressure to give the crude product which was purified using flash column chromatography with hexane-ethyl acetate (9:1) to give (±)-6-(ethoxycarbonylmethyl)-1,4-dioxaspiro[4.5]decane (4.59 g, 74% yield) as a colourless oil. Rf 0.18 (hexane-ethyl acetate, 9:1). The mixture was heated to reflux in a Dean Stark apparatus for 4 h quenched with sodium bicarbonate (5 g) The organic phase was separated from the aqueous phase which was extracted with ethyl acetate (3×100 ml) The combined organic phases were washed with a saturated sodium bicarbonate solution (100 ml) and brine (100 ml) The organic phase was dried over magnesium sulphate the solvent was evaporated under reduced pressure to give the crude product which was purified

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

実験手順: Under an argon atmosphere, ethylene glycol (7.6 ml, 135.87 mmol) and para-toluenesulfonic acid (516 mg, 2.72 mmol) were added to a solution of (±)-2-(ethoxycarbonylmethyl)cyclohexanone (5.00 g, 27.17 mmol) in toluene (136 ml). The mixture was heated to reflux in a Dean Stark apparatus for 4 h and then allowed to cool to room temperature and quenched with sodium bicarbonate (5 g) and a saturated sodium bicarbonate solution (150 ml). The organic phase was separated from the aqueous phase which was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with a saturated sodium bicarbonate solution (100 ml) and brine (100 ml). The organic phase was dried over magnesium sulphate and the solvent was evaporated under reduced pressure to give the crude product which was purified using flash column chromatography with hexane-ethyl acetate (9:1) to give (±)-6-(ethoxycarbonylmethyl)-1,4-dioxaspiro[4.5]decane (4.59 g, 74% yield) as a colourless oil. Rf 0.18 (hexane-ethyl acetate, 9:1). The mixture was heated to reflux in a Dean Stark apparatus for 4 h quenched with sodium bicarbonate (5 g) The organic phase was separated from the aqueous phase which was extracted with ethyl acetate (3×100 ml) The combined organic phases were washed with a saturated sodium bicarbonate solution (100 ml) and brine (100 ml) The organic phase was dried over magnesium sulphate the solvent was evaporated under reduced pressure to give the crude product which was purified

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

実験手順: 8.0 Parts of 4-chloro-2-fluorophenylhydrazine and 9.2 parts of ethyl 2-cyclohexanoneacetate [bp 92°-93°, 0.5 mm Hg; prepared by the method described by A. Sergre, et al., J. Amer. Chem. Soc., 79 3503 (1957)] were dissolved in 75 parts of glacial acetic acid, and the resulting solution was refluxed for 16 hours. The reaction solvent was removed under a reduced pressure of 300 mm Hg, and the residual brown oil was dissolved in 150 parts of methylene chloride. The organic solution was washed with saturated aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate and the solvent was removed under a reduced pressure of 300 mm Hg to give 2-(4-chloro-2-fluorophenyl)-4,4a,5,6,7,8-hexahydro-3(2H)-cinnolinone as a brown oil that solidified on scratching. Purification was achieved by recrystallization from cyclohexane to yield 5.9 parts of tan solid, mp 110°-112°. prepared by the method the resulting solution was refluxed for 16 hours The reaction solvent was removed under a reduced pressure of 300 mm Hg the residual brown oil was dissolved in 150 parts of methylene chloride The organic solution was washed with saturated aqueous sodium bicarbonate solution dried with anhydrous magnesium sulfate the solvent was removed under a reduced pressure of 300 mm Hg

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

実験手順: The chlorination of ethyl(2-oxo-cyclohexyl)-acetate takes place in a manner similar to that described above for the preparation of 2-tert-butyl-6-chloro-cyclohexanone. The title compound is reacted as a crude product without further characterization.

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: The chlorination of ethyl(2-oxo-cyclohexyl)-acetate takes place in a manner similar to that described above for the preparation of 2-tert-butyl-6-chloro-cyclohexanone. The title compound is reacted as a crude product without further characterization.

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

実験手順: A mixture of 1-(4-fluorophenyl)hydrazine hydrochloride (5 g), ethyl 2-cyclohexanoneacetate (5.6 g) and 2-propanol (100 ml) is refluxed under nitrogen for 9 hours. After cooling the mixture is filtered and the solution evaporated to dryness. The residue is purified through a silica gel column eluiting with methylene chloride/methanol (100/1) to give 4 g of isopropyl 6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl-acetate. is refluxed under nitrogen for 9 hours After cooling the mixture is filtered the solution evaporated to dryness The residue is purified through a silica gel column