2-Trifluoromethyl-5-bromoanisole

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 mL round-bottomed flask was added 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (12 mL, 50 mmol) and DMF (4.0 mL, 50 mmol). The solution was stirred at 0° C. and treated with sodium methoxide (4 g, 75 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours. The resulting milky suspension was quenched with ice at 0° C. and the separated aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated sodium chloride (1×25 mL), dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane) to provide 4-bromo-2-methoxy-1-(trifluoromethyl)benzene (5.80 g, 46% yield) as a light yellow oil. m/z (%): 256.1.2 (100%, M++H). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours The resulting milky suspension was quenched with ice at 0° C. the separated aqueous layer was extracted with EtOAc (3×50 mL) The combined organic layers were washed with saturated sodium chloride (1×25 mL) dried over Na2SO4 concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 mL round-bottomed flask was added 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (12 mL, 50 mmol) and DMF (4.0 mL, 50 mmol). The solution was stirred at 0° C. and treated with sodium methoxide (4 g, 75 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours. The resulting milky suspension was quenched with ice at 0° C. and the separated aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated sodium chloride (1×25 mL), dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane) to provide 4-bromo-2-methoxy-1-(trifluoromethyl)benzene (5.80 g, 46% yield) as a light yellow oil. m/z (%): 256.1.2 (100%, M++H). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours The resulting milky suspension was quenched with ice at 0° C. the separated aqueous layer was extracted with EtOAc (3×50 mL) The combined organic layers were washed with saturated sodium chloride (1×25 mL) dried over Na2SO4 concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane)

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 mL round-bottomed flask was added 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (12 mL, 50 mmol) and DMF (4.0 mL, 50 mmol). The solution was stirred at 0° C. and treated with sodium methoxide (4 g, 75 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours. The resulting milky suspension was quenched with ice at 0° C. and the separated aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated sodium chloride (1×25 mL), dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane) to provide 4-bromo-2-methoxy-1-(trifluoromethyl)benzene (5.80 g, 46% yield) as a light yellow oil. m/z (%): 256.1.2 (100%, M++H). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours The resulting milky suspension was quenched with ice at 0° C. the separated aqueous layer was extracted with EtOAc (3×50 mL) The combined organic layers were washed with saturated sodium chloride (1×25 mL) dried over Na2SO4 concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 mL round-bottomed flask was added 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (12 mL, 50 mmol) and DMF (4.0 mL, 50 mmol). The solution was stirred at 0° C. and treated with sodium methoxide (4 g, 75 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours. The resulting milky suspension was quenched with ice at 0° C. and the separated aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated sodium chloride (1×25 mL), dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane) to provide 4-bromo-2-methoxy-1-(trifluoromethyl)benzene (5.80 g, 46% yield) as a light yellow oil. m/z (%): 256.1.2 (100%, M++H). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours The resulting milky suspension was quenched with ice at 0° C. the separated aqueous layer was extracted with EtOAc (3×50 mL) The combined organic layers were washed with saturated sodium chloride (1×25 mL) dried over Na2SO4 concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane)