ethyl 2-cyclohexyl-2-oxoacetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl cyclohexyloxoacetate (46 g) in MeOH (25 mL) was added water (60 mL) and NaOH (50% 20 mL) at 0-15° C. The reaction mixture was heated to 60° C. for 1.5 h. The reaction mixture was cooled with ice-water bath, and acidified with 15% HCl till pH 1. The mixture was extracted with ethyl acetate (2×250 mL). The extracts were washed with brine, dried with sodium sulfate. The drying agent was removed by filtration and the solvent was removed to give a low melting solid (39 g, 99%). 1H NMR: δ 1.15-1.40 (m, 5H,), 1.62-1.96 (m, 5H). 3.20 (m, 1H), 9.4 (s, 1H). 13C-NMR δ, 25.93, 25.76, 27.89, 45.04, 160.90, 198.29. The reaction mixture was cooled with ice-water bath The mixture was extracted with ethyl acetate (2×250 mL) The extracts were washed with brine dried with sodium sulfate The drying agent was removed by filtration the solvent was removed

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

実験手順: Cyclohexyl magnesium bromide (Aldrich) in ether (2 M, 150 mL) was pumped under vacuum to remove ethyl ether, at rt, the residue obtained was then dissolved in anhydrous THF (100 mL) while cooled with an ice water bath. The solution was then added to a solution of diethyl oxalate (60 g ) in THF (150 mL) at -30--40° C. in 10 min. The reaction mixture was warmed to 0° C. for 5 min, and quenched with 10% HCl (100 mL), extracted with ethyl acetate (200 mL), the extract was washed with water (30 mL), brine (50 mL) and dried with sodium sulfate, then filtered. The filtrate was concentrated to give an oil. It was distilled 40-50° C. at 1 mm Hg to remove the starting material and the left over is the product (total of 46 g, 86% yield, purity >90%, it can be distilled at 1 mm Hg, 75-80° C.). 1H NMR δ: 1.20-1.40 (m, 8H), 1.62-1.94 (m, 5H), 3.02 (broad s, 1H), 4.30 (q, J=8 Hz, 2H). 13C-NMR δ 13.91, 25.11, 25.58, 27.36, 46.13, 62.07, 161.84, 197.51. to remove ethyl ether at rt, the residue obtained while cooled with an ice water bath quenched with 10% HCl (100 mL) extracted with ethyl acetate (200 mL) the extract was washed with water (30 mL), brine (50 mL) dried with sodium sulfate filtered The filtrate was concentrated to give an oil It was distilled 40-50° C. at 1 mm Hg to remove the starting material the left the product (total of 46 g, 86% yield, purity >90%, it can be distilled at 1 mm Hg, 75-80° C.)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl cyclohexyloxoacetate (46 g) in MeOH (25 mL) was added water (60 mL) and NaOH (50% 20 mL) at 0-15° C. The reaction mixture was heated to 60° C. for 1.5 h. The reaction mixture was cooled with ice-water bath, and acidified with 15% HCl till pH 1. The mixture was extracted with ethyl acetate (2×250 mL). The extracts were washed with brine, dried with sodium sulfate. The drying agent was removed by filtration and the solvent was removed to give a low melting solid (39 g, 99%). 1H NMR: δ 1.15-1.40 (m, 5H,), 1.62-1.96 (m, 5H). 3.20 (m, 1H), 9.4 (s, 1H). 13C-NMR δ 25.93, 25.76, 27.89, 45.04, 160.90, 198.29. The reaction mixture was cooled with ice-water bath The mixture was extracted with ethyl acetate (2×250 mL) The extracts were washed with brine dried with sodium sulfate The drying agent was removed by filtration the solvent was removed

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

実験手順: Cyclohexyl magnesium bromide (Aldrich) in ether (2 M, 150 mL) was pumped under vacuum to remove ethyl ether, at rt, the residue obtained was then dissolved in anhydrous THF (100 mL) while cooled with an ice water bath. The solution was then added to a solution of diethyl oxalate (60 g) in THF (150 mL) at -30--40° C. in 10 min. The reaction mixture was warmed to 0° C. for 5 min, and quenched with 10% HCl (100 mL), extracted with ethyl acetate (200 mL), the extract was washed with water (30 mL), brine (50 mL) and dried with sodium sulfate, then filtered. The filtrate was concentrated to give an oil. It was distilled 40-50° C. at 1 mm Hg to remove the starting material and the left over is the product (total of 46 g, 86% yield, purity>90%, it can be distilled at 1 mm Hg, 75-80° C.): 1H NMR δ 1.20-1.40 (m, 8H), 1.62-1.94 (m, 5H), 3.02 (broad s, 1H), 4.30 (q, J=8 Hz, 2H). 13C-NMR δ 13.91, 25.11, 25.58, 27.36, 46.13, 62.07, 161.84, 197.51. to remove ethyl ether at rt, the residue obtained while cooled with an ice water bath quenched with 10% HCl (100 mL) extracted with ethyl acetate (200 mL) the extract was washed with water (30 mL), brine (50 mL) dried with sodium sulfate filtered The filtrate was concentrated to give an oil It was distilled 40-50° C. at 1 mm Hg to remove the starting material the left the product (total of 46 g, 86% yield, purity>90%, it can be distilled at 1 mm Hg, 75-80° C.)

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

実験手順: Cyclohexyl magnesium bromide (Aldrich) in ether (2 M, 150 mL) was pumped under vacuum to remove ethyl ether, at rt, the residue obtained was then dissolved in anhydrous THF (100 mL) while cooled with an ice water bath. The solution was then added to a solution of diethyl oxalate (60 g) in THF (150 mL) at -30--40° C. in 10 min. The reaction mixture was warmed to 0° C. for 5 min, and quenched with 10% HCl (100 mL), extracted with ethyl acetate (200 mL), the extract was washed with water (30 mL), brine (50 mL) and dried with sodium sulfate, then filtered. The filtrate was concentrated to give an oil. It was distilled 40-50° C. at 1 mm Hg to remove the starting material and the left over is the product (total of 46 g, 86% yield, purity>90%, it can be distilled at 1 mm Hg, 75-80° C.): 1H NMR δ 1.20-1.40 (m, 8H), 1.62-1.94 (m, 5H), 3.02 (broad s, 1H), 4.30 (q, J=8 Hz, 2H). 13C-NMR δ 13.91, 25.11, 25.58, 27.36, 46.13, 62.07, 161.84, 197.51. to remove ethyl ether at rt, the residue obtained while cooled with an ice water bath quenched with 10% HCl (100 mL) extracted with ethyl acetate (200 mL) the extract was washed with water (30 mL), brine (50 mL) dried with sodium sulfate filtered The filtrate was concentrated to give an oil It was distilled 40-50° C. at 1 mm Hg to remove the starting material the left the product (total of 46 g, 86% yield, purity>90%, it can be distilled at 1 mm Hg, 75-80° C.)

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

実験手順: To a suspension of magnesium turnings (2.20 g, 90.32 mmol) in THF (100 mL) was added cyclohexyl bromide (9.27 mL, 75.27 mmol). The mixture was sonicated (note 1) for 30 min, the supernatant liquid was decanted into an addition funnel and added to a solution of diethyloxalate (22.0 g, 146.14 mmol) in THF (240 mL) at −10° C. over one hour. After 30 minutes, 10% HCl (75 mL) was added the mixture was and stirred 15 minutes. Layers were separated and the aqueous layer was extracted with Et2O (100 mL). Combined organics were washed (brine), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.15-1.40 (m, 5H) 1.56-1.94 (m, 8H) 2.97-3.05 (m, 1H) 4.30 (q, J=7.32 Hz, 2H). The mixture was sonicated (note 1) for 30 min the supernatant liquid was decanted into an addition funnel Layers were separated the aqueous layer was extracted with Et2O (100 mL) Combined organics were washed (brine) dried over Na2SO4 concentrated in vacuo The residue was purified by flash chromatography (EtOAc/hexanes)

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

実験手順: To a suspension of magnesium turnings (2.20 g, 90.32 mmol) in THF (100 mL) was added cyclohexyl bromide (9.27 mL, 75.27 mmol). The mixture was sonicated (note 1) for 30 min, the supernatant liquid was decanted into an addition funnel and added to a solution of diethyloxalate (22.0 g, 146.14 mmol) in THF (240 mL) at −10° C. over one hour. After 30 minutes, 10% HCl (75 mL) was added the mixture was and stirred 15 minutes. Layers were separated and the aqueous layer was extracted with Et2O (100 mL). Combined organics were washed (brine), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.15-1.40 (m, 5H) 1.56-1.94 (m, 8H) 2.97-3.05 (m, 1H) 4.30 (q, J=7.32 Hz, 2H). The mixture was sonicated (note 1) for 30 min the supernatant liquid was decanted into an addition funnel Layers were separated the aqueous layer was extracted with Et2O (100 mL) Combined organics were washed (brine) dried over Na2SO4 concentrated in vacuo The residue was purified by flash chromatography (EtOAc/hexanes)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl cyclohexyloxoacetate (46 g) in MeOH (25 mL) was added water (60 mL) and NaOH (50% 20 mL) at 0-15° C. The reaction mixture was heated to 60° C. for 1.5 h. The reaction mixture was cooled with ice-water bath, and acidified with 15% HCl till pH 1. The mixture was extracted with ethyl acetate (2×250 mL). The extracts were washed with brine, dried with sodium sulfate. The drying agent was removed by filtration and the solvent was removed to give a low melting solid (39 g, 99%). 1H NMR: δ 1.15-1.40 (m, 5H,), 1.62-1.96 (m, 5H). 3.20 (m, 1H), 9.4 (s, 1H). 13C-NMR δ, 25.93, 25.76, 27.89, 45.04, 160.90, 198.29. The reaction mixture was cooled with ice-water bath The mixture was extracted with ethyl acetate (2×250 mL) The extracts were washed with brine dried with sodium sulfate The drying agent was removed by filtration the solvent was removed

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

実験手順: Cyclohexyl magnesium bromide (Aldrich) in ether (2 M, 150 mL) was pumped under vacuum to remove ethyl ether, at rt, the residue obtained was then dissolved in anhydrous THF (100 mL) while cooled with an ice water bath. The solution was then added to a solution of diethyl oxalate (60 g ) in THF (150 mL) at -30--40° C. in 10 min. The reaction mixture was warmed to 0° C. for 5 min, and quenched with 10% HCl (100 mL), extracted with ethyl acetate (200 mL), the extract was washed with water (30 mL), brine (50 mL) and dried with sodium sulfate, then filtered. The filtrate was concentrated to give an oil. It was distilled 40-50° C. at 1 mm Hg to remove the starting material and the left over is the product (total of 46 g, 86% yield, purity >90%, it can be distilled at 1 mm Hg, 75-80° C.). 1H NMR δ: 1.20-1.40 (m, 8H), 1.62-1.94 (m, 5H), 3.02 (broad s, 1H), 4.30 (q, J=8 Hz, 2H). 13C-NMR δ 13.91, 25.11, 25.58, 27.36, 46.13, 62.07, 161.84, 197.51. to remove ethyl ether at rt, the residue obtained while cooled with an ice water bath quenched with 10% HCl (100 mL) extracted with ethyl acetate (200 mL) the extract was washed with water (30 mL), brine (50 mL) dried with sodium sulfate filtered The filtrate was concentrated to give an oil It was distilled 40-50° C. at 1 mm Hg to remove the starting material the left the product (total of 46 g, 86% yield, purity >90%, it can be distilled at 1 mm Hg, 75-80° C.)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl cyclohexyloxoacetate (46 g) in MeOH (25 mL) was added water (60 mL) and NaOH (50% 20 mL) at 0-15° C. The reaction mixture was heated to 60° C. for 1.5 h. The reaction mixture was cooled with ice-water bath, and acidified with 15% HCl till pH 1. The mixture was extracted with ethyl acetate (2×250 mL). The extracts were washed with brine, dried with sodium sulfate. The drying agent was removed by filtration and the solvent was removed to give a low melting solid (39 g, 99%). 1H NMR: δ 1.15-1.40 (m, 5H,), 1.62-1.96 (m, 5H). 3.20 (m, 1H), 9.4 (s, 1H). 13C-NMR δ, 25.93, 25.76, 27.89, 45.04, 160.90, 198.29. The reaction mixture was cooled with ice-water bath The mixture was extracted with ethyl acetate (2×250 mL) The extracts were washed with brine dried with sodium sulfate The drying agent was removed by filtration the solvent was removed