1,5-dibromo-3,3-dimethylpentane

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: Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.5 g, 1.13 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.113 g, 2.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 3,3-dimethyl-1,5-dibromopentane (0.322 g, 1.25 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate (230 mg). The reaction mixture was stirred an additional 1 h at 0° C. The reaction mixture was extracted with EtOAc (3×20 mL) the combined organic phases were washed with water (3×20 mL) and brine (20 mL) dried over MgSO4 The volatiles were removed under reduced pressure the residue was purified by flash column chromatography

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

実験手順: A solution of 24 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 480 ml. of dimethylformamide is treated under argon at -10° C. with 0.16 mol. of sodium hydride (7.0 g. of a 55% dispersion in mineral oil) and then stirred in an ice-bath for 15 minutes. To this, 62 g. of 1,5-dibromo-3,3-dimethylpentane are added in one batch at -5° C., the mixture is then stirred for 1 hour at room temperature and subsequently heated for 18 hours at 60° C. After cooling, the mixture is poured into 4 liters of ice-water, 200 g. of sodium chloride are added, and the separated product is immediately extracted with methylene chloride. The organic phase, shielded from daylight, is washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated to dryness under reduced pressure. The resulting oily residue is chromatographed on 1000 g. of silica gel with methylene chloride as the eluant, care being taken that the eluate is shielded from daylight. The homogeneous fractions are combined, evaporated, and the solid residue recrystallized from ethanol, and there is obtained 2-(5-bromo-3,3-dimethylpentyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester having a melting point of 87°-88° C. the mixture is then stirred for 1 hour at room temperature After cooling the separated product is immediately extracted with methylene chloride is washed with a saturated solution of sodium chloride dried over sodium sulfate concentrated to dryness under reduced pressure The resulting oily residue is chromatographed on 1000 g evaporated the solid residue recrystallized from ethanol

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: Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.5 g, 1.13 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.113 g, 2.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 3,3-dimethyl-1,5-dibromopentane (0.322 g, 1.25 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate (230 mg). The reaction mixture was stirred an additional 1 h at 0° C. The reaction mixture was extracted with EtOAc (3×20 mL) the combined organic phases were washed with water (3×20 mL) and brine (20 mL) dried over MgSO4 The volatiles were removed under reduced pressure the residue was purified by flash column chromatography

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

実験手順: A solution of 24 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 480 ml. of dimethylformamide is treated under argon at -10° C. with 0.16 mol. of sodium hydride (7.0 g. of a 55% dispersion in mineral oil) and then stirred in an ice-bath for 15 minutes. To this, 62 g. of 1,5-dibromo-3,3-dimethylpentane are added in one batch at -5° C., the mixture is then stirred for 1 hour at room temperature and subsequently heated for 18 hours at 60° C. After cooling, the mixture is poured into 4 liters of ice-water, 200 g. of sodium chloride are added, and the separated product is immediately extracted with methylene chloride. The organic phase, shielded from daylight, is washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated to dryness under reduced pressure. The resulting oily residue is chromatographed on 1000 g. of silica gel with methylene chloride as the eluant, care being taken that the eluate is shielded from daylight. The homogeneous fractions are combined, evaporated, and the solid residue recrystallized from ethanol, and there is obtained 2-(5-bromo-3,3-dimethylpentyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester having a melting point of 87°-88° C. the mixture is then stirred for 1 hour at room temperature After cooling the separated product is immediately extracted with methylene chloride is washed with a saturated solution of sodium chloride dried over sodium sulfate concentrated to dryness under reduced pressure The resulting oily residue is chromatographed on 1000 g evaporated the solid residue recrystallized from ethanol

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

実験手順: A solution of 24 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 480 ml. of dimethylformamide is treated under argon at -10° C. with 0.16 mol. of sodium hydride (7.0 g. of a 55% dispersion in mineral oil) and then stirred in an ice-bath for 15 minutes. To this, 62 g. of 1,5-dibromo-3,3-dimethylpentane are added in one batch at -5° C., the mixture is then stirred for 1 hour at room temperature and subsequently heated for 18 hours at 60° C. After cooling, the mixture is poured into 4 liters of ice-water, 200 g. of sodium chloride are added, and the separated product is immediately extracted with methylene chloride. The organic phase, shielded from daylight, is washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated to dryness under reduced pressure. The resulting oily residue is chromatographed on 1000 g. of silica gel with methylene chloride as the eluant, care being taken that the eluate is shielded from daylight. The homogeneous fractions are combined, evaporated, and the solid residue recrystallized from ethanol, and there is obtained 2-(5-bromo-3,3-dimethylpentyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester having a melting point of 87°-88° C. the mixture is then stirred for 1 hour at room temperature After cooling the separated product is immediately extracted with methylene chloride is washed with a saturated solution of sodium chloride dried over sodium sulfate concentrated to dryness under reduced pressure The resulting oily residue is chromatographed on 1000 g evaporated the solid residue recrystallized from ethanol

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

実験手順: A solution of 24 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 480 ml. of dimethylformamide is treated under argon at -10° C. with 0.16 mol. of sodium hydride (7.0 g. of a 55% dispersion in mineral oil) and then stirred in an ice-bath for 15 minutes. To this, 62 g. of 1,5-dibromo-3,3-dimethylpentane are added in one batch at -5° C., the mixture is then stirred for 1 hour at room temperature and subsequently heated for 18 hours at 60° C. After cooling, the mixture is poured into 4 liters of ice-water, 200 g. of sodium chloride are added, and the separated product is immediately extracted with methylene chloride. The organic phase, shielded from daylight, is washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated to dryness under reduced pressure. The resulting oily residue is chromatographed on 1000 g. of silica gel with methylene chloride as the eluant, care being taken that the eluate is shielded from daylight. The homogeneous fractions are combined, evaporated, and the solid residue recrystallized from ethanol, and there is obtained 2-(5-bromo-3,3-dimethylpentyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester having a melting point of 87°-88° C. the mixture is then stirred for 1 hour at room temperature After cooling the separated product is immediately extracted with methylene chloride is washed with a saturated solution of sodium chloride dried over sodium sulfate concentrated to dryness under reduced pressure The resulting oily residue is chromatographed on 1000 g evaporated the solid residue recrystallized from ethanol

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

実験手順: A solution of 24 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 480 ml. of dimethylformamide is treated under argon at -10° C. with 0.16 mol. of sodium hydride (7.0 g of a 55% dispersion in mineral oil) and then stirred in an ice-bath for 15 minutes. To this, 62 g. of 1,5-dibromo-3,3-dimethylpentane are added in one batch at -5° C., the mixture is then stirred for 1 hour at room temperature and subsequently heated for 18 hours at 60° C. After cooling, the mixture is poured into 4 liters of ice-water, 200 g. of sodium chloride are added, and the separated product is immediately extracted with methylene chloride. The organic phase, shielded from daylight, is washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated to dryness under reduced pressure. The resulting oily residue is chromatographed on 1000 g. of silica gel with methylene chloride as the eluant, care being taken that the eluate is shielded from daylight. The homogeneous fractions are combined, evaporated, and the solid residue recrystallized from ethanol, and there is obtained 2-(5-bromo-3,3-dimethylpentyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester having a melting point of 87°-88° C. subsequently heated for 18 hours at 60° C After cooling the separated product is immediately extracted with methylene chloride is washed with a saturated solution of sodium chloride dried over sodium sulfate concentrated to dryness under reduced pressure The resulting oily residue is chromatographed on 1000 g evaporated the solid residue recrystallized from ethanol

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

実験手順: Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.5 g, 1.13 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.113 g, 2.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 3,3-dimethyl-1,5-dibromopentane (0.322 g, 1.25 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate (230 mg). The reaction mixture was stirred an additional 1 h at 0° C. The reaction mixture was extracted with EtOAc (3×20 mL) the combined organic phases were washed with water (3×20 mL) and brine (20 mL) dried over MgSO4 The volatiles were removed under reduced pressure the residue was purified by flash column chromatography

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

実験手順: Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.5 g, 1.13 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.113 g, 2.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 3,3-dimethyl-1,5-dibromopentane (0.322 g, 1.25 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate (230 mg). The reaction mixture was stirred an additional 1 h at 0° C. The reaction mixture was extracted with EtOAc (3×20 mL) the combined organic phases were washed with water (3×20 mL) and brine (20 mL) dried over MgSO4 The volatiles were removed under reduced pressure the residue was purified by flash column chromatography

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

実験手順: Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.5 g, 1.13 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.113 g, 2.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 3,3-dimethyl-1,5-dibromopentane (0.322 g, 1.25 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate (230 mg). The reaction mixture was stirred an additional 1 h at 0° C. The reaction mixture was extracted with EtOAc (3×20 mL) the combined organic phases were washed with water (3×20 mL) and brine (20 mL) dried over MgSO4 The volatiles were removed under reduced pressure the residue was purified by flash column chromatography