4-氟-2-(三氟甲基)苯胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-fluoro-2-(trifluoromethyl)aniline (4.4 g, 24.6 mmol), 2,5-hexanedione (2.8 g, 24.5 mmol) and acetic acid (0.28 mL) was heated to 100° C. After 3 h the reaction mixture was cooled and partitioned between EtOAc and water. The organic layer was separated, dried (MgSO4), and concentrated in vacuo. The residue was purified by flash chromatography (SiO2), eluting with EtOAc/Hex (0:100 to 10:90) to afford 1-[4-fluoro-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole as a yellow oil (3.19 g, 50%); 1H NMR (CDCl3): δ 7.52 (dd, J=8, 3 Hz, 1H), 7.35 (dt, J=3, 8 Hz, 1H), 7.25 (dd, J=5, 8 Hz, 1H), 5.90 (s, 2H), 1.91 (s, 6H); MS (ESI) m/z 258 [M+H]+. After 3 h the reaction mixture was cooled partitioned between EtOAc and water The organic layer was separated dried (MgSO4) concentrated in vacuo The residue was purified by flash chromatography (SiO2) eluting with EtOAc/Hex (0:100 to 10:90)

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: 2.21 g (10 mmol) of 4-chlorosulfonylbenzoic acid is suspended under exclusion of moisture in 30 ml of dichloromethane, the suspension is cooled to -5° C. and, at this temperature, a solution of 1.79 g (10 mmol) of 4-fluoro-2-(trifluoromethyl)aniline and 1 ml of pyridine in 20 ml of dichloromethane is added dropwise thereto. After this dropwise addition has been completed, the mixture is allowed to warm up to room temperature and is agitated for another 12 hours. The thus-produced precipitate is suctioned off and extracted with ether. This ether extract and the filtrate are evaporated together, and the residue is dissolved in dichloroethane. The solution is extracted three times with respectively 10 ml of saturated sodium bicarbonate solution. The combined aqueous extracts are acidified with 2N hydrochloric acid and the thus-precipitated product is removed by filtration. The filter residue is dried under vacuum at 50° C., thus obtaining 3.3 g (9.08 mmol)=90.84% of theory. After this dropwise addition to warm up to room temperature extracted with ether This ether extract the filtrate are evaporated together the residue is dissolved in dichloroethane The solution is extracted three times with respectively 10 ml of saturated sodium bicarbonate solution the thus-precipitated product is removed by filtration The filter residue is dried under vacuum at 50° C. thus obtaining 3.3 g (9.08 mmol)=90.84% of theory

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

实验步骤: 2.21 g (10 mmol) of 4-chlorosulfonylbenzoic acid is suspended under exclusion of moisture in 30 ml of dichloromethane, the suspension is cooled to -5° C. and, at this temperature, a solution of 1.79 g (10 mmol) of 4-fluoro-2-(trifluoromethyl)aniline and 1 ml of pyridine in 20 ml of dichloromethane is added dropwise thereto. After this dropwise addition has been completed, the mixture is allowed to warm up to room temperature and is agitated for another 12 hours. The thus-produced precipitate is suctioned off and extracted with ether. This ether extract and the filtrate are evaporated together, and the residue is dissolved in dichloroethane. The solution is extracted three times with respectively 10 ml of saturated sodium bicarbonate solution. The combined aqueous extracts are acidified with 2N hydrochloric acid and the thus-precipitated product is removed by filtration. The filter residue is dried under vacuum at 50° C., thus obtaining 3.3 g (9.08 mmol)=90.84% of theory. After this dropwise addition to warm up to room temperature extracted with ether This ether extract the filtrate are evaporated together the residue is dissolved in dichloroethane The solution is extracted three times with respectively 10 ml of saturated sodium bicarbonate solution the thus-precipitated product is removed by filtration The filter residue is dried under vacuum at 50° C. thus obtaining 3.3 g (9.08 mmol)=90.84% of theory

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5 g (27.64 mmol) of 4-fluoro-2-(trifluoromethyl)aniline is dissolved in 25 ml of dry pyridine, and the solution is cooled to 0° C. While maintaining the temperature, a solution of 4.82 g (27.4 mmol) of chlorosulfonylacetic acid methyl ester in 20 ml of dichloromethane is added dropwise to the cooled solution during the course of about 10 minutes. Then the mixture is stirred for 6 hours at room temperature. The reaction solution is then diluted with 100 ml of dichloromethane, the pyridine is extracted by shaking with 2N hydrochloride acid, the organic phase is dried over magnesium sulfate, filtered, and evaporated to dryness. The residue is crystallized from diethyl ether/hexane 1:1, thus obtaining 7.35 g (23.32 mmol)=84.35% of theory of a crystallized product, mp 84°14 86° C. While maintaining the temperature the pyridine is extracted by shaking with 2N hydrochloride acid the organic phase is dried over magnesium sulfate filtered evaporated to dryness The residue is crystallized from diethyl ether/hexane 1:1 thus obtaining 7.35 g (23.32 mmol)=84.35% of theory of a crystallized product, mp 84°14 86° C.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5 g (27.64 mmol) of 4-fluoro-2-(trifluoromethyl)aniline is dissolved in 25 ml of dry pyridine, and the solution is cooled to 0° C. While maintaining the temperature, a solution of 4.82 g (27.4 mmol) of chlorosulfonylacetic acid methyl ester in 20 ml of dichloromethane is added dropwise to the cooled solution during the course of about 10 minutes. Then the mixture is stirred for 6 hours at room temperature. The reaction solution is then diluted with 100 ml of dichloromethane, the pyridine is extracted by shaking with 2N hydrochloride acid, the organic phase is dried over magnesium sulfate, filtered, and evaporated to dryness. The residue is crystallized from diethyl ether/hexane 1:1, thus obtaining 7.35 g (23.32 mmol)=84.35% of theory of a crystallized product, mp 84°14 86° C. While maintaining the temperature the pyridine is extracted by shaking with 2N hydrochloride acid the organic phase is dried over magnesium sulfate filtered evaporated to dryness The residue is crystallized from diethyl ether/hexane 1:1 thus obtaining 7.35 g (23.32 mmol)=84.35% of theory of a crystallized product, mp 84°14 86° C.

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

实验步骤: 250 ml of dichloromethane is combined with 9.38 g (52.37 mmol) of 4-fluoro-2-trifluoromethylaniline and 6 ml (14.3 mmol) of pyridine. The mixture is cooled with ice water and under agitation and exclusion of moisture, 13.52 g (57.62 mmol) of 2-chlorosulfonylbenzoic acid methyl ester is added in small increments. The mixture is agitated overnight, washed with 2N hydrochloric acid and water, the dichloromethane solution is dried over sodium sulfate and concentrated to dryness under vacuum. The residue is crystallized from ethyl acetate/hexane. The title compound melts at 143°-145° C. is added in small increments washed with 2N hydrochloric acid and water the dichloromethane solution is dried over sodium sulfate concentrated to dryness under vacuum The residue is crystallized from ethyl acetate/hexane