ethyl 2-bromo-2-cyclohexylacetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 1.0 g (4.4 mmol) 2-(4-chlorophenyl)benzimidazole (commercially available) in 10 mL N,N-dimethylformamide, 4.6 g (14.0 mmol) cesium carbonate and 3.3 g (13.1 mmol) bromo-cyclohexyl-acetic acid ethyl ester (commercially available) were added and the brown suspension was stirred for 22 h at 100° C. After cooling to room temperature the reaction was poured on water and extracted three times with ethyl acetate. The organic phases were washed with water and brine, dried over magnesium sulfate and filtered. To the filtrate silica gel was added and the solvent evaporated. The adsorbed crude product was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate 100:0 to 50:50) to give the desired compound as a colorless solid (58%). MS (Turbo Spray): m/z=397.2 [M+H]. After cooling to room temperature the reaction was poured on water extracted three times with ethyl acetate The organic phases were washed with water and brine dried over magnesium sulfate filtered To the filtrate silica gel was added the solvent evaporated The adsorbed crude product was purified by silica gel chromatography eluting with a gradient of n-heptane:ethyl acetate 100:0 to 50:50)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 75 g (0.28 mol) 2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole in 750 mL N,N-dimethylformamide 116 g (0.33 mol) cesium carbonate and 88 g (0.35 mol) bromo-cyclohexyl-acetic acid ethyl ester (commercially available) were added. The mixture was heated to 100° C. and after stirring for 90 min. another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 6 h another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 22 h (total reaction time) the reaction mixture was cooled to 30° C. and was poured on 1 L ice water and 2 L ethyl acetate. The phases were separated and the aqueous phase extracted with 500 mL ethyl acetate. The combined organic phases were washed three times with 500 mL ice water and once with brine, dried over magnesium sulfate and filtered. To the solution, silica gel was added and the solvent evaporated. The crude adsorbed product was purified by column chromatography over silica gel using n-heptane:ethyl acetate (9:1 v/v) as eluant. The product-containing fractions were pooled and the solvent evaporated until a suspension had formed. The suspension was cooled in an ice bath and filtered to give 92 g (75%) of the desired product as colorless solid. MS (Turbo Spray): 433.1 [M+H]. were added After 22 h (total reaction time) the reaction mixture was cooled to 30° C. The phases were separated the aqueous phase extracted with 500 mL ethyl acetate The combined organic phases were washed three times with 500 mL ice water once with brine, dried over magnesium sulfate filtered To the solution, silica gel was added the solvent evaporated was purified by column chromatography over silica gel the solvent evaporated until a suspension had formed The suspension was cooled in an ice bath filtered

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 1.0 g (4.4 mmol) 2-(4-chlorophenyl)benzimidazole (commercially available) in 10 mL N,N-dimethylformamide, 4.6 g (14.0 mmol) cesium carbonate and 3.3 g (13.1 mmol) bromo-cyclohexyl-acetic acid ethyl ester (commercially available) were added and the brown suspension was stirred for 22 h at 100° C. After cooling to room temperature the reaction was poured on water and extracted three times with ethyl acetate. The organic phases were washed with water and brine, dried over magnesium sulfate and filtered. To the filtrate silica gel was added and the solvent evaporated. The adsorbed crude product was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate 100:0 to 50:50) to give the desired compound as a colorless solid (58%). MS (Turbo Spray): m/z=397.2 [M+H]. After cooling to room temperature the reaction was poured on water extracted three times with ethyl acetate The organic phases were washed with water and brine dried over magnesium sulfate filtered To the filtrate silica gel was added the solvent evaporated The adsorbed crude product was purified by silica gel chromatography eluting with a gradient of n-heptane:ethyl acetate 100:0 to 50:50)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 75 g (0.28 mol) 2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole in 750 mL N,N-dimethylformamide 116 g (0.33 mol) cesium carbonate and 88 g (0.35 mol) bromo-cyclohexyl-acetic acid ethyl ester (commercially available) were added. The mixture was heated to 100° C. and after stirring for 90 min. another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 6 h another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 22 h (total reaction time) the reaction mixture was cooled to 30° C. and was poured on 1 L ice water and 2 L ethyl acetate. The phases were separated and the aqueous phase extracted with 500 mL ethyl acetate. The combined organic phases were washed three times with 500 mL ice water and once with brine, dried over magnesium sulfate and filtered. To the solution, silica gel was added and the solvent evaporated. The crude adsorbed product was purified by column chromatography over silica gel using n-heptane:ethyl acetate (9:1 v/v) as eluant. The product-containing fractions were pooled and the solvent evaporated until a suspension had formed. The suspension was cooled in an ice bath and filtered to give 92 g (75%) of the desired product as colorless solid. MS (Turbo Spray): 433.1 [M+H]. were added After 22 h (total reaction time) the reaction mixture was cooled to 30° C. The phases were separated the aqueous phase extracted with 500 mL ethyl acetate The combined organic phases were washed three times with 500 mL ice water once with brine, dried over magnesium sulfate filtered To the solution, silica gel was added the solvent evaporated was purified by column chromatography over silica gel the solvent evaporated until a suspension had formed The suspension was cooled in an ice bath filtered

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 75 g (0.28 mol) 2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole in 750 mL N,N-dimethylformamide 116 g (0.33 mol) cesium carbonate and 88 g (0.35 mol) bromo-cyclohexyl-acetic acid ethyl ester (commercially available) were added. The mixture was heated to 100° C. and after stirring for 90 min. another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 6 h another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 22 h (total reaction time) the reaction mixture was cooled to 30° C. and was poured on 1 L ice water and 2 L ethyl acetate. The phases were separated and the aqueous phase extracted with 500 mL ethyl acetate. The combined organic phases were washed three times with 500 mL ice water and once with brine, dried over magnesium sulfate and filtered. To the solution, silica gel was added and the solvent evaporated. The crude adsorbed product was purified by column chromatography over silica gel using n-heptane:ethyl acetate (9:1 v/v) as eluant. The product-containing fractions were pooled and the solvent evaporated until a suspension had formed. The suspension was cooled in an ice bath and filtered to give 92 g (75%) of the desired product as colorless solid. MS (Turbo Spray): 433.1 [M+H]. were added After 22 h (total reaction time) the reaction mixture was cooled to 30° C. The phases were separated the aqueous phase extracted with 500 mL ethyl acetate The combined organic phases were washed three times with 500 mL ice water once with brine, dried over magnesium sulfate filtered To the solution, silica gel was added the solvent evaporated was purified by column chromatography over silica gel the solvent evaporated until a suspension had formed The suspension was cooled in an ice bath filtered

反応条件: temp:0.00; pressure:0.00; stir:

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: Into 15 ml of anhydrous ethanol, 205 mg (0.0089 mole) of methallic sodium was dissolved and then, 1.8 g (0.0089 mole) of p-phenoxyphenol was added. The mixture was stirred at room temperature for about 30 minutes. Ethanol was distilled off under a reduced pressure and 5 ml of dimethyl formamide was added to the residue and dimethyl formamide was distilled off under a reduced pressure and then, 15 ml of dimethyl formamide was added to the residue to dissolve it. Into the solution, 2.5 g (0.010 mole) of ethyl α-bromo-α-cyclohexylacetate was added. The mixture was refluxed for 8 hours and then diemethyl formamide was distilled off under a reduced pressure. The residue was admixed with 50 ml of water and extracted twice with 50 ml of benzene. The benzene layers were combined and washed three times with 30 ml of 5% NaOH aq.sol. and then with water and dehydrated over sodium sulfate and distilled in vacuum to obtain 1.4 g of ethyl α-(p-phenoxyphenoxy)α-cyclohexylacetate (yield: 42.6%). Ethanol was distilled off under a reduced pressure and 5 ml of dimethyl formamide was added to the residue and dimethyl formamide was distilled off under a reduced pressure 15 ml of dimethyl formamide was added to the residue to dissolve it The mixture was refluxed for 8 hours was distilled off under a reduced pressure extracted twice with 50 ml of benzene washed three times with 30 ml of 5% NaOH aq.sol distilled in vacuum

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

実験手順: This compound was synthesized in analogy to example 22, intermediate b, from 2-(4-chloro-phenyl)-1H-benzoimidazole (commercially available), bromo-cyclohexyl-acetic acid ethyl ester (commercially available) and cesium carbonate, to provide the final compound as a colorless solid (58%).

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 75 g (0.28 mol) 2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole in 750 ml N,N-dimethylformamide 116 g (0.33 mol) cesium carbonate and 88 g (0.35 mol) bromo-cyclohexyl-acetic acid ethyl ester (commercially available) were added. The mixture was heated to 100° C. and after stirring for 90 min. another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 6 h another 116 g cesium carbonate and 88 g bromo-cyclohexyl-acetic acid ethyl ester were added. After 22 h (total reaction time) the reaction mixture was cooled to 30° C. and was poured on 1 L ice water and 2 L ethyl acetate. The phases were separated and the aqueous phase extracted with 500 mL ethyl acetate. The combined organic phases were washed three times with 500 ml ice water and once with brine, dried over magnesium sulfate and filtered. To the solution, silica gel was added and the solvent evaporated. The crude adsorbed product was purified by column chromatography over silica gel using n-heptane:ethyl acetate (9:1 v/v) as eluant. The product-containing fractions were pooled and the solvent evaporated until a suspension had formed. The suspension was cooled in an ice bath and filtered to give 92 g (75%) of the desired product as colorless solid. were added After 22 h (total reaction time) the reaction mixture was cooled to 30° C. The phases were separated the aqueous phase extracted with 500 mL ethyl acetate The combined organic phases were washed three times with 500 ml ice water once with brine, dried over magnesium sulfate filtered To the solution, silica gel was added the solvent evaporated was purified by column chromatography over silica gel the solvent evaporated until a suspension had formed The suspension was cooled in an ice bath filtered