(4-Bromo-2-(trifluoromethoxy)phenyl)methanol

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

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

Procedure: Add (4-bromo-2-(trifluoromethoxy)phenyl)methanol (9.757 g, 36 mmol) and dichloromethane (180 mL) to a 500 mL flask equipped with a magnetic stir bar and N2 inlet. Cool the solution to 0° C. and then treat with triphenylphosphine (11.33 g, 43 mmol) and carbon tetrabromide (14.26 g, 43 mmol). Stir the reaction at 0° C. for 45 minutes, warm to room temperature and stir an additional 1 hour. Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL), then dry over anhydrous magnesium sulfate. Filter through Celite® and concentrate under vacuum to dryness. Dissolve the residue in hexanes, filter to remove the triphenyl phosphine oxide, and concentrate to a colorless oil. Purify the crude product via silica gel chromatography eluting with hexanes to afford 10.5 g (88%) of the product as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.46-7.40 (m, 2H), 7.38-7.33 (m, 1H), 4.46 (s, 3H). equipped with a magnetic stir bar and N2 inlet the reaction at 0° C. for 45 minutes warm to room temperature stir an additional 1 hour Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL) dry over anhydrous magnesium sulfate Filter through Celite® concentrate under vacuum to dryness Dissolve the residue in hexanes filter to remove the triphenyl phosphine oxide concentrate to a colorless 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:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add (4-bromo-2-(trifluoromethoxy)phenyl)methanol (9.757 g, 36 mmol) and dichloromethane (180 mL) to a 500 mL flask equipped with a magnetic stir bar and N2 inlet. Cool the solution to 0° C. and then treat with triphenylphosphine (11.33 g, 43 mmol) and carbon tetrabromide (14.26 g, 43 mmol). Stir the reaction at 0° C. for 45 minutes, warm to room temperature and stir an additional 1 hour. Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL), then dry over anhydrous magnesium sulfate. Filter through Celite® and concentrate under vacuum to dryness. Dissolve the residue in hexanes, filter to remove the triphenyl phosphine oxide, and concentrate to a colorless oil. Purify the crude product via silica gel chromatography eluting with hexanes to afford 10.5 g (88%) of the product as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.46-7.40 (m, 2H), 7.38-7.33 (m, 1H), 4.46 (s, 3H). equipped with a magnetic stir bar and N2 inlet the reaction at 0° C. for 45 minutes warm to room temperature stir an additional 1 hour Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL) dry over anhydrous magnesium sulfate Filter through Celite® concentrate under vacuum to dryness Dissolve the residue in hexanes filter to remove the triphenyl phosphine oxide concentrate to a colorless oil Purify the crude product via silica gel chromatography eluting with hexanes

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

Procedure: Add (4-bromo-2-(trifluoromethoxy)phenyl)methanol (9.757 g, 36 mmol) and dichloromethane (180 mL) to a 500 mL flask equipped with a magnetic stir bar and N2 inlet. Cool the solution to 0° C. and then treat with triphenylphosphine (11.33 g, 43 mmol) and carbon tetrabromide (14.26 g, 43 mmol). Stir the reaction at 0° C. for 45 minutes, warm to room temperature and stir an additional 1 hour. Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL), then dry over anhydrous magnesium sulfate. Filter through Celite® and concentrate under vacuum to dryness. Dissolve the residue in hexanes, filter to remove the triphenyl phosphine oxide, and concentrate to a colorless oil. Purify the crude product via silica gel chromatography eluting with hexanes to afford 10.5 g (88%) of the product as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.46-7.40 (m, 2H), 7.38-7.33 (m, 1H), 4.46 (s, 3H). equipped with a magnetic stir bar and N2 inlet the reaction at 0° C. for 45 minutes warm to room temperature stir an additional 1 hour Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL) dry over anhydrous magnesium sulfate Filter through Celite® concentrate under vacuum to dryness Dissolve the residue in hexanes filter to remove the triphenyl phosphine oxide concentrate to a colorless oil Purify the crude product via silica gel chromatography eluting with hexanes

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

Procedure: To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzaldehyde (5.0 g, 19 mmol) from Step 1 above in EtOH (100 mL) at 0° C. was added NaBH4 (0.88 g, 23 mmol). The mixture was stirred for 1 h at 0° C., the cooling bath was removed, and the solution was stirred at ambient temperature for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (75 mL). The organic phase was separated, dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using a gradient elution of 5-10% EtOAc:hexanes. 4-Bromo-2-(trifluoromethoxy)benzyl alcohol was obtained as an amorphous solid by evaporation from CH2Cl2 (TLC Rf =0.25 (10% EtOAc:hexanes); HPLC retention time=8.8 min (method A)). the cooling bath was removed the solution was stirred at ambient temperature for 14 h The solvent was removed under reduced pressure the residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (75 mL) The organic phase was separated dried (MgSO4) filtered the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography a gradient elution of 5-10% EtOAc

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

Procedure: To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzaldehyde (5.0 g, 19 mmol) from Step 1 above in EtOH (100 mL) at 0° C. was added NaBH4 (0.88 g, 23 mmol). The mixture was stirred for 1 h at 0° C., the cooling bath was removed, and the solution was stirred at ambient temperature for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (75 mL). The organic phase was separated, dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using a gradient elution of 5-10% EtOAc:hexanes. 4-Bromo-2-(trifluoromethoxy)benzyl alcohol was obtained as an amorphous solid by evaporation from CH2Cl2 (TLC Rf =0.25 (10% EtOAc:hexanes); HPLC retention time=8.8 min (method A)). the cooling bath was removed the solution was stirred at ambient temperature for 14 h The solvent was removed under reduced pressure the residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (75 mL) The organic phase was separated dried (MgSO4) filtered the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography a gradient elution of 5-10% EtOAc

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

Procedure: To a stirred solution of 4-bromo-2-(trifluoro-methoxy)benzaldehyde (5.0 g, 19 mmol) from Step 1 above in EtOH (100 mL) at 0° C. was added NaBH4 (0.88 g, 23 mmol). The mixture was stirred for 1 h at 0° C., the cooling bath was removed, and the solution was stirred at ambient temperature for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (75 mL). The organic phase was separated, dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using a gradient elution of 5-10% EtOAc:hexanes. 4-Bromo-2-(trifluoromethoxy)benzyl alcohol was obtained as an amorphous solid by evaporation from CH2Cl2 (TLC Rf =0.25 (10% EtOAc:hexanes); HPLC retention time=8.8 min (method A)). the cooling bath was removed the solution was stirred at ambient temperature for 14 h The solvent was removed under reduced pressure the residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (75 mL) The organic phase was separated dried (MgSO4) filtered the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography a gradient elution of 5-10% EtOAc

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

Procedure: Add (4-bromo-2-(trifluoromethoxy)phenyl)methanol (9.757 g, 36 mmol) and dichloromethane (180 mL) to a 500 mL flask equipped with a magnetic stir bar and N2 inlet. Cool the solution to 0° C. and then treat with triphenylphosphine (11.33 g, 43 mmol) and carbon tetrabromide (14.26 g, 43 mmol). Stir the reaction at 0° C. for 45 minutes, warm to room temperature and stir an additional 1 hour. Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL), then dry over anhydrous magnesium sulfate. Filter through Celite® and concentrate under vacuum to dryness. Dissolve the residue in hexanes, filter to remove the triphenyl phosphine oxide, and concentrate to a colorless oil. Purify the crude product via silica gel chromatography eluting with hexanes to afford 10.5 g (88%) of the product as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.46-7.40 (m, 2H), 7.38-7.33 (m, 1H), 4.46 (s, 3H). equipped with a magnetic stir bar and N2 inlet the reaction at 0° C. for 45 minutes warm to room temperature stir an additional 1 hour Wash the reaction with water (2×180 mL) and saturated sodium chloride solution (1×180 mL) dry over anhydrous magnesium sulfate Filter through Celite® concentrate under vacuum to dryness Dissolve the residue in hexanes filter to remove the triphenyl phosphine oxide concentrate to a colorless oil Purify the crude product via silica gel chromatography eluting with hexanes