4-bromo-1-methyl-2-(trifluoromethyl)benzene

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

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

Procedure: N-Bromosuccinimide (2.6 g) and 2,2′-azobis(isobutyronitrile) (35 mg) were added to a solution of 5-bromo-2-methylbenzotrifluoride (CAS #86845-27-4, 3.5 g) in carbon tetrachloride (35 mL), and the mixture was heated under reflux for five hours. The reaction solution was ice-cooled and then the insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent: heptane) to obtain 3.86 g of the title compound. The property values of the compound are as follows. the mixture was heated under reflux for five hours cooled the insoluble matter was removed by filtration The filtrate was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent: heptane)

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

Procedure: N-Bromosuccinimide (2.6 g) and 2,2′-azobis(isobutyronitrile) (35 mg) were added to a solution of 5-bromo-2-methylbenzotrifluoride (CAS #86845-27-4, 3.5 g) in carbon tetrachloride (35 mL), and the mixture was heated under reflux for five hours. The reaction solution was ice-cooled and then the insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent: heptane) to obtain 3.86 g of the title compound. The property values of the compound are as follows. the mixture was heated under reflux for five hours cooled the insoluble matter was removed by filtration The filtrate was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent: heptane)

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

Procedure: 4-Bromo-1-methyl-2-trifluoromethyl-benzene (3 g, 12.55 mmol), N-bromosuccinimide (2.68 g, 15.06 mmol, 1.2 eq) and dibenzoylperoxid (60 mg, 2.5 mmol, 0.02 eq) are stirred in carbon tetrachloride under ultraviolet light at reflux for 5 h. The reaction mixture is cooled to RT, filtered and the filtrate is concentrated in vacuo. The residue is carefully purified by chromatography (silicagel, pure hexanes) to afford the title compound as a colorless liquid. at reflux for 5 h filtered the filtrate is concentrated in vacuo The residue is carefully purified by chromatography (silicagel, pure hexanes)

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

Procedure: 4-Bromo-1-methyl-2-trifluoromethyl-benzene (3 g, 12.55 mmol), N-bromosuccinimide (2.68 g, 15.06 mmol, 1.2 eq) and dibenzoylperoxid (60 mg, 2.5 mmol, 0.02 eq) are stirred in carbon tetrachloride under ultraviolet light at reflux for 5 h. The reaction mixture is cooled to RT, filtered and the filtrate is concentrated in vacuo. The residue is carefully purified by chromatography (silicagel, pure hexanes) to afford the title compound as a colorless liquid. at reflux for 5 h filtered the filtrate is concentrated in vacuo The residue is carefully purified by chromatography (silicagel, pure hexanes)

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-Bromo-1-methyl-2-trifluoromethyl-benzene (3.4 g, 14.2 mmol) in THF was added n-BuLi at −78° C. After the reaction mixture was stirred at −78° C. for 30 minutes, dry acetone was slowly added. The resulting content was maintained at −78° C. for 3 hours and slowly warmed up to RT overnight. The reaction mixture was then partitioned between ethyl acetate and water. The ethyl acetate layer was then washed with brine, dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude oil. The crude solid was purified via flash chromatography (15% EtOAc in n-hexane) yielded the title compound as an oil (2.7 g, 86%). The resulting content was maintained at −78° C. for 3 hours slowly warmed up to RT overnight The reaction mixture was then partitioned between ethyl acetate and water The ethyl acetate layer was then washed with brine dried over Na2SO4 filtered the solvent evaporated in vacuo to yield a crude oil The crude solid was purified via flash chromatography (15% EtOAc in n-hexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-Bromo-1-methyl-2-trifluoromethyl-benzene (3.4 g, 14.2 mmol) in THF was added n-BuLi at −78° C. After the reaction mixture was stirred at −78° C. for 30 minutes, dry acetone was slowly added. The resulting content was maintained at −78° C. for 3 hours and slowly warmed up to RT overnight. The reaction mixture was then partitioned between ethyl acetate and water. The ethyl acetate layer was then washed with brine, dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude oil. The crude solid was purified via flash chromatography (15% EtOAc in n-hexane) yielded the title compound as an oil (2.7 g, 86%). The resulting content was maintained at −78° C. for 3 hours slowly warmed up to RT overnight The reaction mixture was then partitioned between ethyl acetate and water The ethyl acetate layer was then washed with brine dried over Na2SO4 filtered the solvent evaporated in vacuo to yield a crude oil The crude solid was purified via flash chromatography (15% EtOAc in n-hexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-Bromo-1-methyl-2-trifluoromethyl-benzene (3.4 g, 14.2 mmol) in THF was added n-BuLi at −78° C. After the reaction mixture was stirred at −78° C. for 30 minutes, dry acetone was slowly added. The resulting content was maintained at −78° C. for 3 hours and slowly warmed up to RT overnight. The reaction mixture was then partitioned between ethyl acetate and water. The ethyl acetate layer was then washed with brine, dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude oil. The crude solid was purified via flash chromatography (15% EtOAc in n-hexane) yielded the title compound as an oil (2.7 g, 86%). The resulting content was maintained at −78° C. for 3 hours slowly warmed up to RT overnight The reaction mixture was then partitioned between ethyl acetate and water The ethyl acetate layer was then washed with brine dried over Na2SO4 filtered the solvent evaporated in vacuo to yield a crude oil The crude solid was purified via flash chromatography (15% EtOAc in n-hexane)

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

Procedure: A solution of commercially available 4-bromo-1-methyl-2-(trifluoromethyl)benzene (1 eq.), NBS (1.1 eq.) and a catalytic amount of benzoyl peroxide in CCl4 (0.21M) was stirred at room temperature for 1 h under a 150 W spot lamp. The mixture was concentrated, purification by column chromatography on silica gel, eluting with Hex, afforded the desired material as an oil. The mixture was concentrated purification by column chromatography on silica gel eluting with Hex

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

Procedure: After N-bromosuccinimide (1.49 g, 6.63 mmol) and 2,2′-azobis(isbutyronitrile) (20 mg) were added to a solution of 4-bromo-1-methyl-2-(trifluoromethyl)benzene (2.0 g, 8.4 mmol) in carbon tetrachloride (20 ml), the mixture was heated under reflux for 5 hours. The temperature of the reaction mixture was returned to room temperature and the residue obtained by removing the solvent under reduced pressure was subjected to silica gel column chromatography (eluting solvent: n-hexane) to give crude 4-bromo-1-bromomethyl-2-(trifluoromethyl)benzene. Potassium cyanide (365 mg, 5.6 mmol) was added to a solution of crude 4-bromo-1-bromomethyl-2-(trifluoromethyl)benzene obtained in the above in a mixture of ethanol-water (3:1, 12 ml), and the mixture was stirred at 70° C. for 3 hours. After the reaction mixture was poured into water and extracted with ethyl acetate, the organic layer was washed with a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=10/1-5/1) to give [4-bromo-2-(trifluoromethyl)phenyl]acetonitrile as a solid (1.14 g, total yield: 52%). the mixture was heated under reflux for 5 hours was returned to room temperature the residue obtained by removing the solvent under reduced pressure was subjected to silica gel column chromatography (eluting solvent: n-hexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-Bromo-1-methyl-2-trifluoromethyl-benzene (3.4 g, 14.2 mmol) in THF was added n-BuLi at −78° C. After the reaction mixture was stirred at −78° C. for 30 minutes, dry acetone was slowly added. The resulting content was maintained at −78° C. for 3 hours and slowly warmed up to RT overnight. The reaction mixture was then partitioned between ethyl acetate and water. The ethyl acetate layer was then washed with brine, dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude oil. The crude solid was purified via flash chromatography (15% EtOAc in n-hexane) yielded the title compound as an oil (2.7 g, 86%) The resulting content was maintained at −78° C. for 3 hours slowly warmed up to RT overnight The reaction mixture was then partitioned between ethyl acetate and water The ethyl acetate layer was then washed with brine dried over Na2SO4 filtered the solvent evaporated in vacuo to yield a crude oil The crude solid was purified via flash chromatography (15% EtOAc in n-hexane)