3,5-二氟-2-(三氟甲基)苯胺

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 200 ml of tetrahydrofuran and 50 g of 2,4,6-trifluorobenzotrifluoride were initially introduced into a stainless steel autoclave and it was pressurized using 30 ml of liquid ammonia. Subsequently, the mixture was heated at 120° C. for 6 hours with stirring. After cooling and releasing the pressure, the reaction mixture was subjected to a fractional distillation. 15 g of 2-amino-4,6-difluoro-benzotrifluoride were obtained at a boiling point of 57° to 58° C. at 12 mbar. After a small intermediate run, 32 g of 2,6-difluoro-4-amino-benzotrifluoride passed over at a boiling point of 103° to 105° C. at 16 mbar. The melting point of the 2,6-difluoro-4-amino-benzotrifluoride obtained was 66° C. After cooling the reaction mixture was subjected to a fractional distillation

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 200 ml of tetrahydrofuran and 50 g of 2,4,6-trifluorobenzotrifluoride were initially introduced into a stainless steel autoclave and it was pressurized using 30 ml of liquid ammonia. Subsequently, the mixture was heated at 120° C. for 6 hours with stirring. After cooling and releasing the pressure, the reaction mixture was subjected to a fractional distillation. 15 g of 2-amino-4,6-difluoro-benzotrifluoride were obtained at a boiling point of 57° to 58° C. at 12 mbar. After a small intermediate run, 32 g of 2,6-difluoro-4-amino-benzotrifluoride passed over at a boiling point of 103° to 105° C. at 16 mbar. The melting point of the 2,6-difluoro-4-amino-benzotrifluoride obtained was 66° C. After cooling the reaction mixture was subjected to a fractional distillation

反应条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 3,5-difluoro-2-(trifluoromethyl)aniline (24, 1.0 g, 5.07 mmol) in a 48% aqueous HBr (8 mL) and H2O (8 mL) was stirred at −5° C. for 5 min. To the suspension, NaNO2 (350 mg, 5.07 mmol) was added in a 10 mL aqueous solution dropwise maintaining −5° C. The resulting mixture was stirred at −5° C. for 1 h then CuBr (1.09 g, 7.63 mmol) was added portion-wise and the resulting suspension was allowed to slowly warm to ambient temperature. After 4 hours, the resulting solution was extracted with hexanes (3×75 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was chromatographed over silica gel (40 g Redisep column, pure hexanes) to afford 1-bromo-3,5-difluoro-2-(trifluoromethyl)benzene (25) as a light yellow liquid (1.01 g, 68%). 1H NMR (300 MHz, CDCl3) δ 7.34-7.28 (m, 1H), 6.99-6.85 (m, 1H). dropwise maintaining −5° C The resulting mixture was stirred at −5° C. for 1 h to slowly warm to ambient temperature After 4 hours the resulting solution was extracted with hexanes (3×75 mL) The combined organics were dried over Na2SO4 filtered concentrated under reduced pressure The resulting residue was chromatographed over silica gel (40 g Redisep column, pure hexanes)

反应条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 3,5-difluoro-2-(trifluoromethyl)aniline (24, 1.0 g, 5.07 mmol) in a 48% aqueous HBr (8 mL) and H2O (8 mL) was stirred at −5° C. for 5 min. To the suspension, NaNO2 (350 mg, 5.07 mmol) was added in a 10 mL aqueous solution dropwise maintaining −5° C. The resulting mixture was stirred at −5° C. for 1 h then CuBr (1.09 g, 7.63 mmol) was added portion-wise and the resulting suspension was allowed to slowly warm to ambient temperature. After 4 hours, the resulting solution was extracted with hexanes (3×75 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was chromatographed over silica gel (40 g Redisep column, pure hexanes) to afford 1-bromo-3,5-difluoro-2-(trifluoromethyl)benzene (25) as a light yellow liquid (1.01 g, 68%). 1H NMR (300 MHz, CDCl3) δ 7.34-7.28 (m, 1H), 6.99-6.85 (m, 1H). dropwise maintaining −5° C The resulting mixture was stirred at −5° C. for 1 h to slowly warm to ambient temperature After 4 hours the resulting solution was extracted with hexanes (3×75 mL) The combined organics were dried over Na2SO4 filtered concentrated under reduced pressure The resulting residue was chromatographed over silica gel (40 g Redisep column, pure hexanes)

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 200 ml of tetrahydrofuran and 50 g of 2,4,6-tri-fluorobenzotrifluoride are initially introduced into a stainless steel autoclave, and 30 ml of liquid ammonia are injected. The batch is then heated to 120° C. for 6 hours and with stirring. The reaction mixture is cooled,the pressure is released and the reaction mixture subjected to fractional distillation. At a boiling point of 57° C.-58° C./12 mbar, 15 g of 2-trifluoromethyI-3,5-difluoroaniline are obtained. After a small intermediate fraction 32 g of 3,5-difluoro-4-trifluoromethylaniline distil over at a boiling point of 103° C.-105° C./16 mbar (melting point: 66° C.). the reaction mixture subjected to fractional distillation

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 200 ml of tetrahydrofuran and 50 g of 2,4,6-tri-fluorobenzotrifluoride are initially introduced into a stainless steel autoclave, and 30 ml of liquid ammonia are injected. The batch is then heated to 120° C. for 6 hours and with stirring. The reaction mixture is cooled,the pressure is released and the reaction mixture subjected to fractional distillation. At a boiling point of 57° C.-58° C./12 mbar, 15 g of 2-trifluoromethyI-3,5-difluoroaniline are obtained. After a small intermediate fraction 32 g of 3,5-difluoro-4-trifluoromethylaniline distil over at a boiling point of 103° C.-105° C./16 mbar (melting point: 66° C.). the reaction mixture subjected to fractional distillation

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a stainless steel autoclave, 200 ml of tetrahydrofuran and 50 g of 2,4,6-trifluorobenzotrifluoride are introduced, and 30 ml of liquid ammonia are pressed on. The mixture is then heated at 120° C. for 6 hours, with stirring. The reaction mixture is cooled, the pressure is released, and the mixture is subjected to fractional distillation. At a boiling point of 57° to 58° C. at 12 mbar, 15 g of 2-amino-4,6-difluoro-benzotrifluoride are obtained. After a small intermediate cut, 32 g of 2,6-difluoro-4-amino-benzotrifluoride distil over at a boiling point of 103° to 105° C. at 16 mbar. Melting point of the resultant 2,6-difluoro-4-amino-benzotrifluoride: 66° C. The reaction mixture is cooled the mixture is subjected to fractional distillation

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 200 ml of tetrahydrofuran and 50 g of 2,4,6-trifluorobenzotrifluoride were initially introduced into a stainless steel autoclave and it was pressurized using 30 ml of liquid ammonia. Subsequently, the mixture was heated at 120° C. for 6 hours with stirring. After cooling and releasing the pressure, the reaction mixture was subjected to a fractional distillation. 15 g of 2-amino-4,6-difluoro-benzotrifluoride were obtained at a boiling point of 57° to 58° C. at 12 mbar. After a small intermediate run, 32 g of 2,6-difluoro-4-amino-benzotrifluoride passed over at a boiling point of 103° to 105° C. at 16 mbar. The melting point of the 2,6-difluoro-4-amino-benzotrifluoride obtained was 66° C. After cooling the reaction mixture was subjected to a fractional distillation

反应条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 3,5-difluoro-2-(trifluoromethyl)aniline (24, 1.0 g, 5.07 mmol) in a 48% aqueous HBr (8 mL) and H2O (8 mL) was stirred at −5° C. for 5 min. To the suspension, NaNO2 (350 mg, 5.07 mmol) was added in a 10 mL aqueous solution dropwise maintaining −5° C. The resulting mixture was stirred at −5° C. for 1 h then CuBr (1.09 g, 7.63 mmol) was added portion-wise and the resulting suspension was allowed to slowly warm to ambient temperature. After 4 hours, the resulting solution was extracted with hexanes (3×75 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was chromatographed over silica gel (40 g Redisep column, pure hexanes) to afford 1-bromo-3,5-difluoro-2-(trifluoromethyl)benzene (25) as a light yellow liquid (1.01 g, 68%). 1H NMR (300 MHz, CDCl3) δ 7.34-7.28 (m, 1H), 6.99-6.85 (m, 1H). dropwise maintaining −5° C The resulting mixture was stirred at −5° C. for 1 h to slowly warm to ambient temperature After 4 hours the resulting solution was extracted with hexanes (3×75 mL) The combined organics were dried over Na2SO4 filtered concentrated under reduced pressure The resulting residue was chromatographed over silica gel (40 g Redisep column, pure hexanes)