4-bromo-2-(trifluoromethoxy)aniline

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

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

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: 4-Bromo-2-(trifluoromethoxy)aniline (1.0 g, 3.9 mmol) was dissolved in dry toluene (25 mL), sodium carbonate (0.621 g, 5.86 mmol) and benzyl chloroformate (0.669 mL, 4.69 mmol) was added and the mixture stirred under nitrogen at room temperature for 22 hours. The reaction was then heated to 80° C. and stirred at this temperature for 17 hours and then heated further to reflux and stirred for 22 hours. Water (100 mL) was added to the called mixture, the aqueous phase separated and washed with ethyl acetate (2×100 mL). The combined organic extracts were washed with 0.5 M aq, citric acid (70 mL), water (70 mL), brine (70 mL), dried (MgSO4), filtered and concentrated in vacua to give a pink solid. The crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine) to give the title compound (I46) (1.153 g, 76% yield) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=8.7 Hz, 1H), 7.44-7.36 (m, 7H), 6.95 (s, 1H), 5.22 (s, 2H). LCMS Method C: rt 6.67 min; m/z 389.9 [M−H]−. The reaction was then heated to 80° C. stirred at this temperature for 17 hours heated further to reflux stirred for 22 hours the aqueous phase separated washed with ethyl acetate (2×100 mL) The combined organic extracts were washed with 0.5 M aq citric acid (70 mL), water (70 mL), brine (70 mL), dried (MgSO4) filtered concentrated in vacua to give a pink solid The crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine)

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

Procedure: 4-Bromo-2-(trifluoromethoxy)aniline (1.0 g, 3.9 mmol) was dissolved in dry toluene (25 mL), sodium carbonate (0.621 g, 5.86 mmol) and benzyl chloroformate (0.669 mL, 4.69 mmol) was added and the mixture stirred under nitrogen at room temperature for 22 hours. The reaction was then heated to 80° C. and stirred at this temperature for 17 hours and then heated further to reflux and stirred for 22 hours. Water (100 mL) was added to the called mixture, the aqueous phase separated and washed with ethyl acetate (2×100 mL). The combined organic extracts were washed with 0.5 M aq, citric acid (70 mL), water (70 mL), brine (70 mL), dried (MgSO4), filtered and concentrated in vacua to give a pink solid. The crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine) to give the title compound (I46) (1.153 g, 76% yield) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=8.7 Hz, 1H), 7.44-7.36 (m, 7H), 6.95 (s, 1H), 5.22 (s, 2H). LCMS Method C: rt 6.67 min; m/z 389.9 [M−H]−. The reaction was then heated to 80° C. stirred at this temperature for 17 hours heated further to reflux stirred for 22 hours the aqueous phase separated washed with ethyl acetate (2×100 mL) The combined organic extracts were washed with 0.5 M aq citric acid (70 mL), water (70 mL), brine (70 mL), dried (MgSO4) filtered concentrated in vacua to give a pink solid The crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine)

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

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

Procedure: The title compound (0.294 g) was prepared from 2-trifluoromethoxy-4-bromo aniline (0.5 g, 1.9 mmol) and 2-fluorophenylboronic acid (0.345 g, 2.5 mmol) as a yellow liquid. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): 7.47 (td, J 1.2, 4.7, 1H), 7.33-7.20 (m, 5H), 6.89 (d, J 8.8, 1H), 5.62 (s, 2H).

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl nitrite (1.78 mL, 15.0 mmol), copper (II) chloride (1.61 g, 12.0 mmol) and 4-bromo-2-(trifluoromethoxy)aniline (2.56 g, 10.0 mmol) in acetonitrile (40 mL) was heated to 70° C., stirred for 3 hours, cooled to room temperature, poured into 0.5M HCl, and extracted with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 275 (M+H)+. cooled to room temperature extracted with diethyl ether The combined extracts were washed with water and brine dried (MgSO4) filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl nitrite (1.78 mL, 15.0 mmol), copper (II) chloride (1.61 g, 12.0 mmol) and 4-bromo-2-(trifluoromethoxy)aniline (2.56 g, 10.0 mmol) in acetonitrile (40 mL) was heated to 70° C., stirred for 3 hours, cooled to room temperature, poured into 0.5M HCl, and extracted with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 275 (M+H)+. cooled to room temperature extracted with diethyl ether The combined extracts were washed with water and brine dried (MgSO4) filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl nitrite (1.78 mL, 15.0 mmol), copper (II) chloride (1.61 g, 12.0 mmol) and 4-bromo-2-(trifluoromethoxy)aniline (2.56 g, 10.0 mmol) in acetonitrile (40 mL) was heated to 70° C., stirred for 3 hours, cooled to room temperature, poured into 0.5M HCl, and extracted with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 275 (M+H)+. cooled to room temperature extracted with diethyl ether The combined extracts were washed with water and brine dried (MgSO4) filtered concentrated

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

Procedure: 4-Bromo-2-(trifluoromethoxy)aniline (1.0 g, 3.9 mmol) was dissolved in dry toluene (25 mL), sodium carbonate (0.621 g, 5.86 mmol) and benzyl chloroformate (0.669 mL, 4.69 mmol) was added and the mixture stirred under nitrogen at room temperature for 22 hours. The reaction was then heated to 80° C. and stirred at this. temperature for 17 hours and then heated further to reflux and stirred for 22 hours. Water (100 mL) was added to the coiled mixture, the aqueous phase separated and washed with ethyl acetate (2×100 mL). The combined organic extracts were washed with 0.5 M aq. citric acid (70 mL), water (70 mL), brine (70 mL), dried (MgSO4), filtered and concentrated in vacuo to give a pink solid. The crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine) to give the title compound (I46) (1.153 g, 76% yield) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=8.7 Hz, 1H), 7.44-7.36 (m, 7H), 6.95 (s, 1H), 5.22 (s, 2H). LCMS Method C: rt 6.67 min; m/z 389.9 [M−H]−. The reaction was then heated to 80° C. stirred at this temperature for 17 hours heated further to reflux stirred for 22 hours the aqueous phase separated washed with ethyl acetate (2×100 mL) The combined organic extracts were washed with 0.5 M aq. citric acid (70 mL), water (70 mL), brine (70 mL) dried (MgSO4) filtered concentrated in vacuo to give a pink solid The crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine)