ethyl 3-cyclohexyl-3-oxopropanoate

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

実験手順: To a solution of 3-Cyclohexyl-3-oxo-propionic acid ethyl ester (1.0 g, 5.0 mmol, 1.0 equiv) in THF (5.0 mL) was added 3-Amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (1.17 g, 5.0 mmol, 1.0 equiv) and SnBu2Cl2 (0.15 g, 0.50 mmol, 0.1 equiv) at room temperature. After stirred at room temperature for 5 minutes, the solution was added PhSiH3. The resulting reaction mixture was stirred at 65° C. under N2 for 18 hours, after which the solution was concentrated under vacuum and the residue was purified by silica gel column chromatography EtOAc/heptane, 10-60% to give product (0.7 g). MS: 416 [M+H+]. The resulting reaction mixture was stirred at 65° C. under N2 for 18 hours after which the solution was concentrated under vacuum the residue was purified by silica gel column chromatography EtOAc/heptane, 10-60%

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

実験手順: To ethyl β-oxocyclohexanepropionate (4.4 g, 0.234 mole) in n-propanol (500 ml) is added dropwise with stirring under nitrogen at 80° C. methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during 5 hours, the reaction is cooled and evaporated to a residual oil. Crystallization from ethylacetate gives a white powder mp 170.5° to 172° C. After heating at reflux during 5 hours the reaction is cooled evaporated to a residual oil Crystallization from ethylacetate

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

実験手順: To ethyl β-oxocyclohexanepropionate (4.4 g, 0.234 mole) in n-propanol (500 ml) is added dropwise with stirring under nitrogen at 80° C. methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during 5 hours, the reaction is cooled and evaporated to a residual oil. Crystallization from ethylacetate gives a white powder mp 170.5° C. to 172° C. After heating at reflux during 5 hours the reaction is cooled evaporated to a residual oil Crystallization from ethylacetate

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

実験手順: To ethyl β-oxocyclohexanepropionate (4.4 g, 0.234 mole) in n-propanol (500 ml) is added dropwise with stirring under nitrogen at 80° C. methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during 5 hours, the reaction is cooled and evaporated to a residual oil. Crystallization from ethylacetate gives a white powder mp 170.5° C. to 172° C. After heating at reflux during 5 hours the reaction is cooled evaporated to a residual oil Crystallization from ethylacetate

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

実験手順: To a solution of 3-cyclohexyl-3-oxo-propionic acid ethyl ester 5 (1.6 g, 8.3 mmol) in anhydrous THF (200 mL), cooled at 0° C., NaH (900 mg, 21 mmol) was added. After 15 min 2-bromo-1-pyridin-4-yl-ethanone hydrobromide 1 (3 g, 10.8 mmol) was added and the mixture was stirred 5 h at 0° C. The solvent was removed and the residue was dissolved in EtOH (120 mL). Ammonium acetate (1.9 g, 25 mmol) was added and the solution was stirred overnight at rt. After solvent removal the residue was dissolved in EtOAc and the organic phase was washed with a saturated aqueous solution of Na2CO3, then with water, dried (Na2SO4) and concentrated. The crude material was purified by silica gel chromatography (eluant: EtOAc) to yield 2-cyclohexyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester as a white solid (1.1 g, 43%). The solvent was removed the residue was dissolved in EtOH (120 mL) the solution was stirred overnight at rt After solvent removal the residue was dissolved in EtOAc the organic phase was washed with a saturated aqueous solution of Na2CO3 with water, dried (Na2SO4) concentrated The crude material was purified by silica gel chromatography (eluant: EtOAc)

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

実験手順: An operation similar to that in Example 1 (1) was performed using 2-chloro-4′-(trifluoromethyl)acetophenone (13.4 g) and ethyl 3-cyclohexyl-3-oxopropanoate (9.9 g) to give the title compound (7.7 g, 40%) as a yellow crystal.

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

実験手順: To a solution of ethyl 3-cyclohexyl-3-oxopropanoate (1.0 g, 5.0 mmol) in diethyl ether (15 mL) was added sulfuryl chloride (750 mg, 5.5 mmol) at 0° C., and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (150 mL) were added to the reaction solution, and the mixture was stirred for 30 min. The organic layer was washed with saturated brine (10 mL) and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure to give the title compound (870 mg, 60%) as a colorless oil. the mixture was stirred for 30 min The organic layer was washed with saturated brine (10 mL) dried over anhydrous magnesium sulfate the insoluble material was filtered off The 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 solution of 3-Cyclohexyl-3-oxo-propionic acid ethyl ester (1.0 g, 5.0 mmol, 1.0 equiv) in THF (5.0 mL) was added 3-Amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (1.17 g, 5.0 mmol, 1.0 equiv) and SnBu2Cl2 (0.15 g, 0.50 mmol, 0.1 equiv) at room temperature. After stirred at room temperature for 5 minutes, the solution was added PhSiH3. The resulting reaction mixture was stirred at 65° C. under N2 for 18 hours, after which the solution was concentrated under vacuum and the residue was purified by silica gel column chromatography EtOAc/heptane, 10-60% to give product (0.7 g). MS: 416 [M+H+]. The resulting reaction mixture was stirred at 65° C. under N2 for 18 hours after which the solution was concentrated under vacuum the residue was purified by silica gel column chromatography EtOAc/heptane, 10-60%

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

実験手順: To ethyl β-oxocyclohexanepropionate (4.4 g, 0.234 mole) in n-propanol (500 ml) is added dropwise with stirring under nitrogen at 80° C. methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during 5 hours, the reaction is cooled and evaporated to a residual oil. Crystallization from ethylacetate gives a white powder mp 170.5° to 172° C. After heating at reflux during 5 hours the reaction is cooled evaporated to a residual oil Crystallization from ethylacetate

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

実験手順: To a solution of 3-cyclohexyl-3-oxo-propionic acid ethyl ester 5 (1.6 g, 8.3 mmol) in anhydrous THF (200 mL), cooled at 0° C., NaH (900 mg, 21 mmol) was added. After 15 min 2-bromo-1-pyridin-4-yl-ethanone hydrobromide 1 (3 g, 10.8 mmol) was added and the mixture was stirred 5 h at 0° C. The solvent was removed and the residue was dissolved in EtOH (120 mL). Ammonium acetate (1.9 g, 25 mmol) was added and the solution was stirred overnight at rt. After solvent removal the residue was dissolved in EtOAc and the organic phase was washed with a saturated aqueous solution of Na2CO3, then with water, dried (Na2SO4) and concentrated. The crude material was purified by silica gel chromatography (eluant:EtOAc) to yield 2-cyclohexyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester as a white solid (1.1 g, 43%). The solvent was removed the residue was dissolved in EtOH (120 mL) the solution was stirred overnight at rt After solvent removal the residue was dissolved in EtOAc the organic phase was washed with a saturated aqueous solution of Na2CO3 with water, dried (Na2SO4) concentrated The crude material was purified by silica gel chromatography (eluant:EtOAc)

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

実験手順: To a solution of 3-cyclohexyl-3-oxo-propionic acid ethyl ester 5 (1.6 g, 8.3 mmol) in anhydrous THF (200 mL), cooled at 0° C., NaH (900 mg, 21 mmol) was added. After 15 min 2-bromo-1-pyridin-4-yl-ethanone hydrobromide 1 (3 g, 10.8 mmol) was added and the mixture was stirred 5 h at 0° C. The solvent was removed and the residue was dissolved in EtOH (120 mL). Ammonium acetate (1.9 g, 25 mmol) was added and the solution was stirred overnight at rt. After solvent removal the residue was dissolved in EtOAc and the organic phase was washed with a saturated aqueous solution of Na2CO3, then with water, dried (Na2SO4) and concentrated. The crude material was purified by silica gel chromatography (eluant:EtOAc) to yield 2-cyclohexyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester as a white solid (1.1 g, 43%). The solvent was removed the residue was dissolved in EtOH (120 mL) the solution was stirred overnight at rt After solvent removal the residue was dissolved in EtOAc the organic phase was washed with a saturated aqueous solution of Na2CO3 with water, dried (Na2SO4) concentrated The crude material was purified by silica gel chromatography (eluant:EtOAc)

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

実験手順: To a solution of ethyl 3-cyclohexyl-3-oxopropanoate (1.0 g, 5.0 mmol) in diethyl ether (15 mL) was added sulfuryl chloride (750 mg, 5.5 mmol) at 0° C., and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (150 mL) were added to the reaction solution, and the mixture was stirred for 30 min. The organic layer was washed with saturated brine (10 mL) and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure to give the title compound (870 mg, 60%) as a colorless oil. the mixture was stirred for 30 min The organic layer was washed with saturated brine (10 mL) dried over anhydrous magnesium sulfate the insoluble material was filtered off The filtrate was concentrated under reduced pressure