2-[2-(trifluoromethyl)phenyl]acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Trifluoromethyl)phenylacetonitrile (2.0 g) was dissolved in tetrahydrofuran (50 mL). Potassium tert-butoxide (60.6 mg), 18-crown-6 (2.85 g) and methyl acrylate (973 μL) were added at 0° C. and the mixture was stirred at the same temperature for 40 minutes. The reaction was terminated with saturated ammonium chloride, followed by dilution with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. Concentration under reduced pressure gave an oil. The oil was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 30%) to obtain the title compound (2.2 g). The reaction was terminated with saturated ammonium chloride The organic layer was washed with brine dried over magnesium sulfate Concentration under reduced pressure gave an oil The oil was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 30%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Trifluoromethylphenyl)acetonitrile (3 g) and tetrabutylammonium bisulfate (550 mg) were suspended in toluene (30 mL), and a 50% sodium hydroxide aqueous solution (15 mL) was added dropwise under ice-cooling. After stirring for 10 minutes, (2-bromoethoxy)-tert-butyldimethylsilane (5.2 mL) was added at the same temperature. The mixture was brought back to room temperature and stirred overnight. Water was added to the reaction solution, followed by extraction with tert-butyl methyl ether. The resulting organic layer was washed with brine and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration, and then the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (5 g). The property values of the compound are as follows. cooling was brought back to room temperature stirred overnight followed by extraction with tert-butyl methyl ether The resulting organic layer was washed with brine dried over anhydrous sodium sulfate The drying agent was separated by filtration the organic layer was concentrated under reduced pressure The residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 12.6 g of (2-trifluoromethyl-phenyl)-acetonitrile and 7.6 ml of 1,2-dibromopropane in 36 ml ether were added slowly through a dropping funnel to a suspension of 3.62 g of sodium hydride in 85 ml DMSO at 0° C. After addition, the ice-water bath was allowed to warm up to room temperature slowly and the reaction mixture was stirred at room temperature overnight. The reaction was carefully quenched with isopropyl and H2O. The suspension became clear. The organic layer was separated, and the aqueous layer was extracted twice with ether. The combined organic extracts were combined, dried and concentrated by evaporation in a vacuum. The residue was purified by column chromatography on silica-gel (EtOAc-hexane 2%-4%) to yield 8.5 g of product as a white solid. After addition The reaction was carefully quenched with isopropyl and H2O The organic layer was separated the aqueous layer was extracted twice with ether dried concentrated by evaporation in a vacuum The residue was purified by column chromatography on silica-gel (EtOAc-hexane 2%-4%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 12.6 g of (2-trifluoromethyl-phenyl)-acetonitrile and 7.6 ml of 1,2-dibromopropane in 36 ml ether were added slowly through a dropping funnel to a suspension of 3.62 g of sodium hydride in 85 ml DMSO at 0° C. After addition, the ice-water bath was allowed to warm up to room temperature slowly and the reaction mixture was stirred at room temperature overnight. The reaction was carefully quenched with isopropyl and H2O. The suspension became clear. The organic layer was separated, and the aqueous layer was extracted twice with ether. The combined organic extracts were combined, dried and concentrated by evaporation in a vacuum. The residue was purified by column chromatography on silica-gel (EtOAc-hexane 2%-4%) to yield 8.5 g of product as a white solid. After addition The reaction was carefully quenched with isopropyl and H2O The organic layer was separated the aqueous layer was extracted twice with ether dried concentrated by evaporation in a vacuum The residue was purified by column chromatography on silica-gel (EtOAc-hexane 2%-4%)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Trifluoromethylphenyl)acetonitrile (12.47 g, 67.3 mmol) was dissolved in THF (87.3 mL) at room temperature under nitrogen atmosphere. The reaction solution was cooled to −10° C. Then, potassium tert-butoxide (7.93 g, 70.7 mmol) was added to the reaction solution and the reaction mixture was stirred at −10° C. for 10 minutes. 1-Bromo-3-chloropropane (6.99 mL, 70.7 mmol) was added dropwise to the reaction mixture over 14 minutes, and the reaction mixture was stirred at 0° C. for 2 hours. The reaction was quenched with 10% NH4Cl aq. (8.6 mL). After the mixture was stirred, the aqueous layer was separated. The organic layer was concentrated under the reduced pressure to obtain the title compound (23.24 g). The yield was calculated as over 99% by HPLC external standard method. the reaction mixture was stirred at 0° C. for 2 hours The reaction was quenched with 10% NH4Cl aq. (8.6 mL) After the mixture was stirred the aqueous layer was separated The organic layer was concentrated under the reduced pressure

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Trifluoromethylphenyl)acetonitrile (12.47 g, 67.3 mmol) was dissolved in THF (87.3 mL) at room temperature under nitrogen atmosphere. The reaction solution was cooled to −10° C. Then, potassium tert-butoxide (7.93 g, 70.7 mmol) was added to the reaction solution and the reaction mixture was stirred at −10° C. for 10 minutes. 1-Bromo-3-chloropropane (6.99 mL, 70.7 mmol) was added dropwise to the reaction mixture over 14 minutes, and the reaction mixture was stirred at 0° C. for 2 hours. The reaction was quenched with 10% NH4Cl aq. (8.6 mL). After the mixture was stirred, the aqueous layer was separated. The organic layer was concentrated under the reduced pressure to obtain the title compound (23.24 g). The yield was calculated as over 99% by HPLC external standard method. the reaction mixture was stirred at 0° C. for 2 hours The reaction was quenched with 10% NH4Cl aq. (8.6 mL) After the mixture was stirred the aqueous layer was separated The organic layer was concentrated under the reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Trifluoromethyl)phenylacetonitrile (2.0 g) was dissolved in tetrahydrofuran (50 mL). Potassium tert-butoxide (60.6 mg), 18-crown-6 (2.85 g) and methyl acrylate (973 μL) were added at 0° C. and the mixture was stirred at the same temperature for 40 minutes. The reaction was terminated with saturated ammonium chloride, followed by dilution with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. Concentration under reduced pressure gave an oil. The oil was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 30%) to obtain the title compound (2.2 g). The reaction was terminated with saturated ammonium chloride The organic layer was washed with brine dried over magnesium sulfate Concentration under reduced pressure gave an oil The oil was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 30%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Trifluoromethylphenyl)acetonitrile (3 g) and tetrabutylammonium bisulfate (550 mg) were suspended in toluene (30 mL), and a 50% sodium hydroxide aqueous solution (15 mL) was added dropwise under ice-cooling. After stirring for 10 minutes, (2-bromoethoxy)-tert-butyldimethylsilane (5.2 mL) was added at the same temperature. The mixture was brought back to room temperature and stirred overnight. Water was added to the reaction solution, followed by extraction with tert-butyl methyl ether. The resulting organic layer was washed with brine and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration, and then the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (5 g). The property values of the compound are as follows. cooling was brought back to room temperature stirred overnight followed by extraction with tert-butyl methyl ether The resulting organic layer was washed with brine dried over anhydrous sodium sulfate The drying agent was separated by filtration the organic layer was concentrated under reduced pressure The residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Trifluoromethylphenyl)acetonitrile (3 g) and tetrabutylammonium bisulfate (550 mg) were suspended in toluene (30 mL), and a 50% sodium hydroxide aqueous solution (15 mL) was added dropwise under ice-cooling. After stirring for 10 minutes, (2-bromoethoxy)-tert-butyldimethylsilane (5.2 mL) was added at the same temperature. The mixture was brought back to room temperature and stirred overnight. Water was added to the reaction solution, followed by extraction with tert-butyl methyl ether. The resulting organic layer was washed with brine and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration, and then the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (5 g). The property values of the compound are as follows. cooling was brought back to room temperature stirred overnight followed by extraction with tert-butyl methyl ether The resulting organic layer was washed with brine dried over anhydrous sodium sulfate The drying agent was separated by filtration the organic layer was concentrated under reduced pressure The residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 12.6 g of (2-trifluoromethyl-phenyl)-acetonitrile and 7.6 ml of 1,2-dibromopropane in 36 ml ether were added slowly through a dropping funnel to a suspension of 3.62 g of sodium hydride in 85 ml DMSO at 0° C. After addition, the ice-water bath was allowed to warm up to room temperature slowly and the reaction mixture was stirred at room temperature overnight. The reaction was carefully quenched with isopropyl and H2O. The suspension became clear. The organic layer was separated, and the aqueous layer was extracted twice with ether. The combined organic extracts were combined, dried and concentrated by evaporation in a vacuum. The residue was purified by column chromatography on silica-gel (EtOAc-hexane 2%-4%) to yield 8.5 g of product as a white solid. After addition The reaction was carefully quenched with isopropyl and H2O The organic layer was separated the aqueous layer was extracted twice with ether dried concentrated by evaporation in a vacuum The residue was purified by column chromatography on silica-gel (EtOAc-hexane 2%-4%)