methyl 2-cyclohexylacetate

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 argon, 75 mg (039 mmol) of 5-amino-1-cyclopentyl-1H-pyrazole-4-carboxamide and 183 mg (1.16 mmol, 3 equiv.) of methyl cyclohexylacetate are introduced into 1.5 ml of absolute ethanol. At 0° C., 54 mg of sodium hydride (60% dispersion in mineral oil; L35 mmol, 15 equiv.) are slowly added in a countercurrent of argon. The resulting mixture is slowly heated and stirred under reflux for 18 h. For workup, 20 ml of water are added, and the mixture is extracted several times with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated in vacuo. The crude product is purified by preparative HPLC. The resulting mixture is slowly heated under reflux for 18 h the mixture is extracted several times with ethyl acetate The combined organic phases are dried over sodium sulfate concentrated in vacuo The crude product is purified by preparative HPLC

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

実験手順: To an ice cold suspension of 0.92 g (23 mmol) of sodium hydride (NaH 60% dispersion in mineral oil) (previously washed with hexane and dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) was added 0.9 g (5.76 mmol) of methyl cyclohexylacetate, and the resulting mixture was stirred at 0° C. for 20 min. Then 1.2 g (8.56 mmol) of ethyl 2-furoate was added, and the reaction mixture was heated at reflux overnight. The mixture was then cooled to 0° C., quenched by the addition of 1 M HCl solution to pH=3, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane) to afford 1.1 g (76% yield) of desired 2-cyclohexyl-3-furan-2-yl-3-oxo-propionic acid methyl ester as indicated by 1H NMR. previously washed with hexane dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) the reaction mixture was heated at reflux overnight The mixture was then cooled to 0° C. quenched by the addition of 1 M HCl solution to pH=3 extracted with ethyl acetate The combined organic extracts were washed with brine dried over sodium sulfate concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane)

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

実験手順: To an ice cold suspension of 0.92 g (23 mmol) of sodium hydride (NaH 60% dispersion in mineral oil) (previously washed with hexane and dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) was added 0.9 g (5.76 mmol) of methyl cyclohexylacetate, and the resulting mixture was stirred at 0° C. for 20 min. Then 1.2 g (8.56 mmol) of ethyl 2-furoate was added, and the reaction mixture was heated at reflux overnight. The mixture was then cooled to 0° C., quenched by the addition of 1 M HCl solution to pH=3, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane) to afford 1.1 g (76% yield) of desired 2-cyclohexyl-3-furan-2-yl-3-oxo-propionic acid methyl ester as indicated by 1H NMR. previously washed with hexane dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) the reaction mixture was heated at reflux overnight The mixture was then cooled to 0° C. quenched by the addition of 1 M HCl solution to pH=3 extracted with ethyl acetate The combined organic extracts were washed with brine dried over sodium sulfate concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane)

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

実験手順: A solution of 49.6 g (0.40 mole) dimethyl methylphosphonate (Aldrich) in 500 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 188 ml of 2.34 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 40 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 31.2 g (0.20 mole) methylcyclohexylacetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 25 ml acetic acid and rotary evaporated to a white gel. The gelatenous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3x), the combined organic extracts were backwashed (50 cc H 2 O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 160°-162° (0.2 mm) to give dimethyl 2-oxo-3-cyclohexylpropylphosphonate (2h). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 100 ml portions of chloroform (3x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled

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

実験手順: A solution of 49.6 g (0.40 mole) dimethyl methylphosphonate (Aldrich) in 500 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 188 ml of 2.34 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 40 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 31.2 g (0.20 mole) methylcyclohexylacetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 25 ml acetic acid and rotary evaporated to a white gel. The gelatenous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3x), the combined organic extracts were backwashed (50 cc H 2 O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 160°-162° (0.2 mm) to give dimethyl 2-oxo-3-cyclohexylpropylphosphonate (2h). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 100 ml portions of chloroform (3x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled

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

実験手順: To a stirred solution of diisopropylamine (0.85 ml, 6.10 mmol) in 30 ml tetrahydrofuran at -78° under argon was added n-butyllithium (2.5 ml of a 2.5M solution in hexane). After 0.5 hour, methyl cyclohexylacetate (1 ml, 6.10 mmol) was added dropwise in 10 ml tetrahydrofuran. The solution was stirred for 45 minutes, after which was added acetaldehyde (1 ml) in 10 ml tetrahydrofuran. This solution was stirred for two hours at -78°, warmed to room temperature and stirred an additional 12 hours, quenched with water and acidified with 10% hydrochloric acid. The mixture was extracted twice with ethyl ether, and the combined organic portions were then washed once with 10% hydrochloric acid, twice with water, once with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to give the alcohol as an orange oil (b.p. 85°-92°, 0.5 mm). This solution was stirred for two hours at -78° stirred an additional 12 hours quenched with water The mixture was extracted twice with ethyl ether the combined organic portions were then washed once with 10% hydrochloric acid, twice with water, once with saturated sodium chloride solution dried over magnesium sulfate filtered concentrated

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

実験手順: To a stirred solution of diisopropylamine (0.85 ml, 6.10 mmol) in 30 ml tetrahydrofuran at -78° under argon was added n-butyllithium (2.5 ml of a 2.5M solution in hexane). After 0.5 hour, methyl cyclohexylacetate (1 ml, 6.10 mmol) was added dropwise in 10 ml tetrahydrofuran. The solution was stirred for 45 minutes, after which was added acetaldehyde (1 ml) in 10 ml tetrahydrofuran. This solution was stirred for two hours at -78°, warmed to room temperature and stirred an additional 12 hours, quenched with water and acidified with 10% hydrochloric acid. The mixture was extracted twice with ethyl ether, and the combined organic portions were then washed once with 10% hydrochloric acid, twice with water, once with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to give the alcohol as an orange oil (b.p. 85°-92°, 0.5 mm). This solution was stirred for two hours at -78° stirred an additional 12 hours quenched with water The mixture was extracted twice with ethyl ether the combined organic portions were then washed once with 10% hydrochloric acid, twice with water, once with saturated sodium chloride solution dried over magnesium sulfate filtered concentrated

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

実験手順: To a stirred solution of dimethyl methylphosphonate (10.3 g, 0.083 mol) in 150 ml of anhydrous THF at -78° C. was added dropwise a solution of n-butyl lithium in hexane (1.67N, 50 ml, 0.083 mol) under argon atmosphere. After 30 minutes, a solution of methyl cyclohexylacetate (5.0 g, 0.035 mol) in 10 ml of anhydrous THF was further added and the mixture was stirred for 30 minutes. The reaction solution was allowed to warm to 0° C., diluted with 5 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue, and then the mixture was extracted with ethyl acetate (50 ml×2). The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give a colorless transparent oil of dimethyl 3-cyclohexyl-2-oxopropylphosphonate (7.4 g, 0.0298 mol, yield 85.3%, b.p. 118°-122° C./0.23 mmHg), which was assigned the structure by the following data: concentrated 30 ml of water was added to the residue the mixture was extracted with ethyl acetate (50 ml×2) The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1) dried over anhydrous sodium sulfate concentrated The residue was distilled under reduced pressure

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

実験手順: To an ice-cooled and stirred solution of cyclohexylacetic acid (9.34 g, 0.066 mol) in 30 ml of ether was slowly added an excess solution of diazomethane in ether. After concentration of ether, the residue was distilled under reduced pressure to give a colorless transparent liquid of methyl cyclohexylacetate (7.45 g, 0.048 mol, yield 72.4%, b.p. 86°-88° C./12 mmHg), which was assigned the structure by the following data: After concentration of ether, the residue was distilled under reduced pressure

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyl lithium (2.64 M solution in hexane, 3.8 ml) was added dropwise to a solution of diisopropylamine (1.55 ml) in THF (15 ml) under ice-cooling, and the reaction solution was stirred at the same temperature for 10 minutes. The reaction solution was cooled to −78° C. Then, a solution of methyl cyclohexylacetate (CAS No. 14352-61-5, 500 mg) in THF (3 ml) was added dropwise and the reaction solution was stirred at the same temperature for 30 minutes. Then, 1-chloro-3-iodopropane (CAS No. 6940-76-7, 1.1 ml) was added dropwise to the reaction solution. The reaction solution was stirred at the same temperature for 20 minutes and then gradually heated to room temperature. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was sequentially washed with 1 N hydrochloric acid, water, a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane-diethyl ether system) to obtain 1.00 g of the title compound. The property value of the compound is as follows. cooling the reaction solution was stirred at the same temperature for 30 minutes 6940-76-7, 1.1 ml) was added dropwise to the reaction solution The reaction solution was stirred at the same temperature for 20 minutes gradually heated to room temperature the organic layer was separated The organic layer was sequentially washed with 1 N hydrochloric acid, water a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (elution solvent: hexane-diethyl ether system)

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

実験手順: To an ice cold suspension of 0.92 g (23 mmol) of sodium hydride (NaH 60% dispersion in mineral oil) (previously washed with hexane and dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) was added 0.9 g (5.76 mmol) of methyl cyclohexylacetate, and the resulting mixture was stirred at 0° C. for 20 min. Then 1.2 g (8.56 mmol) of ethyl 2-furoate was added, and the reaction mixture was heated at reflux overnight. The mixture was then cooled to 0° C., quenched by the addition of 1 M HCl solution to pH=3, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane) to afford 1.1 g (76% yield) of desired 2-cyclohexyl-3-furan-2-yl-3-oxo-propionic acid methyl ester as indicated by 1H NMR. previously washed with hexane dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) the reaction mixture was heated at reflux overnight The mixture was then cooled to 0° C. quenched by the addition of 1 M HCl solution to pH=3 extracted with ethyl acetate The combined organic extracts were washed with brine dried over sodium sulfate concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane)