methyl 2-(4-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: Prepared from LiOH hydrolysis of (4-Oxo-Cyclohexyl)-acetic acid methyl ester (commercial available).

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 64.4 g of methyl (4-oxocyclohexyl)acetate and 137.9 g of propyltriphenylphosphonium bromide were introduced into 500 ml of THF, and the mixture was cooled to -10° C. with stirring under nitrogen. A solution of 40.17 g of potassium tert-butoxide in 400 ml of THF was then added dropwise with stirring at the same temperature, and the mixture was then stirred at RT for a further 2 h. Conventional work-up gave methyl (4-propylidenecyclohexyl)acetate. with stirring at the same temperature the mixture was then stirred at RT for a further 2 h

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 64.4 g of methyl (4-oxocyclohexyl)acetate and 137.9 g of propyltriphenylphosphonium bromide were introduced into 500 ml of THF, and the mixture was cooled to -10° C. with stirring under nitrogen. A solution of 40.17 g of potassium tert-butoxide in 400 ml of THF was then added dropwise with stirring at the same temperature, and the mixture was then stirred at RT for a further 2 h. Conventional work-up gave methyl (4-propylidenecyclohexyl)acetate. with stirring at the same temperature the mixture was then stirred at RT for a further 2 h

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

実験手順: A high pressure autoclave was charged with a mixture of methyl (4-hydroxyphenyl)acetate (50 g, 0.30 mol), palladium (5 g) (10%) on carbon (50% wet) and O-xylene (250 mL). The reaction mixture was stirred under 110 to 115 psi of hydrogen pressure for 7 to 8 h at 140° C. The reaction was monitored by HPLC. The reaction mixture was then cooled to room temperature, and the catalyst was filtered off. Filtrate was concentrated under reduced pressure to get 4-(methoxycarbonylmethyl)cyclohexanone as light yellow to colorless oily liquid (48.7 g, 97.4%). the catalyst was filtered off Filtrate was concentrated under reduced pressure

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

実験手順: To a tetrahydrofuran (60 mL) solution of (4-oxo-cyclohexyl)-acetic acid methyl ester (2.14 g) obtained in Example (1c), methylamine (2.0 M tetrahydrofuran solution, 12.5 mL), acetic acid (0.72 mL), and sodium triacetoxyborohydride (2.67 g) were added at room temperature. After 4 hours, the reaction mixture was diluted with saturated sodium bicarbonate (100 mL). The organic solvent was removed under reduced pressure. The aqueous mixture was subjected to extraction with dichloromethane (×3). The dichloromethane layer was dried over sodium sulfate and then concentrated. The residue was purified by column chromatography (NH silica gel, dichloromethane/methanol) to obtain the title compound (822 mg, 35%) as a brown oil. The organic solvent was removed under reduced pressure The aqueous mixture was subjected to extraction with dichloromethane (×3) The dichloromethane layer was dried over sodium sulfate concentrated The residue was purified by column chromatography (NH silica gel, dichloromethane/methanol)

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

実験手順: To a tetrahydrofuran (60 mL) solution of (4-oxo-cyclohexyl)-acetic acid methyl ester (2.14 g) obtained in Example (1c), methylamine (2.0 M tetrahydrofuran solution, 12.5 mL), acetic acid (0.72 mL), and sodium triacetoxyborohydride (2.67 g) were added at room temperature. After 4 hours, the reaction mixture was diluted with saturated sodium bicarbonate (100 mL). The organic solvent was removed under reduced pressure. The aqueous mixture was subjected to extraction with dichloromethane (×3). The dichloromethane layer was dried over sodium sulfate and then concentrated. The residue was purified by column chromatography (NH silica gel, dichloromethane/methanol) to obtain the title compound (822 mg, 35%) as a brown oil. The organic solvent was removed under reduced pressure The aqueous mixture was subjected to extraction with dichloromethane (×3) The dichloromethane layer was dried over sodium sulfate concentrated The residue was purified by column chromatography (NH silica gel, dichloromethane/methanol)

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

実験手順: To a methanol (50 mL) solution of (4-oxo-cyclohexyl)-acetic acid methyl ester (4.18 g) obtained in Example (1c), sodium borohydride (1.86 g) was added in small portions at 0° C. The reaction mixture was stirred for 1 hour and diluted with a 10% aqueous ammonium chloride solution (100 mL). The organic solvent was removed using an evaporator. The remaining aqueous solution was subjected to two extractions with ethyl acetate. The organic layer was washed with saturated brine, then dried over sodium sulfate, and then concentrated to obtain trans-(4-hydroxy-cyclohexyl)-acetic acid methyl ester (2.56 g, 60%) as a colorless oil and cis-4-hydroxy-cyclohexyl)-acetic acid methyl ester (0.517 g, 12%) as a colorless oil. The organic solvent was removed an evaporator The remaining aqueous solution was subjected to two extractions with ethyl acetate The organic layer was washed with saturated brine dried over sodium sulfate concentrated

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

実験手順: A 1 N aqueous hydrochloric acid solution (50 mL)/acetone (200 ml) mixture of (1,4-dioxa-spiro[4.5]dec-8-yl)-acetic acid methyl ester (4.99 g) obtained in Example (1b) was stirred at room temperature for 15 hours. The organic solvent was removed using an evaporator. The remaining aqueous solution was subjected to two extractions with ethyl acetate. The organic layer was washed with saturated brine, then dried over sodium sulfate, and then concentrated to obtain the title compound (4.30 g, quantitative yield) as a colorless oil. The organic solvent was removed an evaporator The remaining aqueous solution was subjected to two extractions with ethyl acetate The organic layer was washed with saturated brine dried over sodium sulfate concentrated

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

実験手順: A 1 N aqueous hydrochloric acid solution (50 mL)/acetone (200 ml) mixture of (1,4-dioxa-spiro[4.5]dec-8-yl)-acetic acid methyl ester (4.99 g) obtained in Example (1b) was stirred at room temperature for 15 hours. The organic solvent was removed using an evaporator. The remaining aqueous solution was subjected to two extractions with ethyl acetate. The organic layer was washed with saturated brine, then dried over sodium sulfate, and then concentrated to obtain the title compound (4.30 g, quantitative yield) as a colorless oil. The organic solvent was removed an evaporator The remaining aqueous solution was subjected to two extractions with ethyl acetate The organic layer was washed with saturated brine dried over sodium sulfate concentrated

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

実験手順: Prepared from LiOH hydrolysis of (4-Oxo-Cyclohexyl)-acetic acid methyl ester (commercial available).

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

実験手順: Prepared from LiOH hydrolysis of (4-Oxo-Cyclohexyl)-acetic acid methyl ester (commercial available).