4-bromo-1-iodo-2-(trifluoromethoxy)benzene

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:

Conditions: temp:-74.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-bromo-1-iodo-2-(trifluoromethoxy)benzene (22.04 g, 60 mmol) to a 1000 mL 3-neck flask equipped with a magnetic stir bar, thermocouple, addition funnel, and N2 inlet and replace the atmosphere in the flask with nitrogen. After adding anhydrous THF (300 mL), cool the mixture to −74° C. and treat dropwise with a solution of t-butyllithium (70 mL of 1.7 M solution, 120 mmol). Stir the resulting solution for 90 minutes and then treated dropwise with a solution of N-formyl morpholine (14.52 g, 126 mmol) in THF (15 mL). Stir the mixture an additional 15 minutes at −74° C. and then allow to warm to 0° C. over 1 hour. Quench the reaction by the adding 0.25 M citric acid (200 mL) and extract with ethyl acetate (1×300 mL). Wash the organic layer with saturated sodium chloride solution (1×200 mL), dry over anhydrous magnesium sulfate, filter through Celite®, and concentrate to an oil. Purify the crude product via silica gel chromatography eluting with hexanes to afford 8.24 g (51%) of the product as white crystals: 1H NMR (300 MHz, CDCl3) δ 10.32 (s, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.63-7.53 (m, 2H). equipped with a magnetic stir bar thermocouple, addition funnel, and N2 inlet Stir the mixture an additional 15 minutes at −74° C. to warm to 0° C. over 1 hour Quench the reaction by the adding 0.25 M citric acid (200 mL) extract with ethyl acetate (1×300 mL) Wash the organic layer with saturated sodium chloride solution (1×200 mL) dry over anhydrous magnesium sulfate filter through Celite® concentrate to an oil Purify the crude product via silica gel chromatography eluting with hexanes

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: Compound 5B was prepared from Compound 5A and 4-bromo-1-iodo-2-trifluoromethoxy-benzene using a the conditions described for Example 1B. MS (electrospray): mass calculated for C21H21BrF3NO2, 455.07; m/z found 456.1 [M+H]+.

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

Procedure: Compound 5B was prepared from Compound 5A and 4-bromo-1-iodo-2-trifluoromethoxy-benzene using a the conditions described for Example 1B. MS (electrospray): mass calculated for C21H21BrF3NO2, 455.07; m/z found 456.1 [M+H]+.

Conditions: temp:-74.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-bromo-1-iodo-2-(trifluoromethoxy)benzene (22.04 g, 60 mmol) to a 1000 mL 3-neck flask equipped with a magnetic stir bar, thermocouple, addition funnel, and N2 inlet and replace the atmosphere in the flask with nitrogen. After adding anhydrous THF (300 mL), cool the mixture to −74° C. and treat dropwise with a solution of t-butyllithium (70 mL of 1.7 M solution, 120 mmol). Stir the resulting solution for 90 minutes and then treated dropwise with a solution of N-formyl morpholine (14.52 g, 126 mmol) in THF (15 mL). Stir the mixture an additional 15 minutes at −74° C. and then allow to warm to 0° C. over 1 hour. Quench the reaction by the adding 0.25 M citric acid (200 mL) and extract with ethyl acetate (1×300 mL). Wash the organic layer with saturated sodium chloride solution (1×200 mL), dry over anhydrous magnesium sulfate, filter through Celite®, and concentrate to an oil. Purify the crude product via silica gel chromatography eluting with hexanes to afford 8.24 g (51%) of the product as white crystals: 1H NMR (300 MHz, CDCl3) δ 10.32 (s, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.63-7.53 (m, 2H). equipped with a magnetic stir bar thermocouple, addition funnel, and N2 inlet Stir the mixture an additional 15 minutes at −74° C. to warm to 0° C. over 1 hour Quench the reaction by the adding 0.25 M citric acid (200 mL) extract with ethyl acetate (1×300 mL) Wash the organic layer with saturated sodium chloride solution (1×200 mL) dry over anhydrous magnesium sulfate filter through Celite® concentrate to an oil Purify the crude product via silica gel chromatography eluting with hexanes