(2-bromo-4-chlorophenyl)methanol

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: Add pyridinium chlorochromate (432 mg, 2 mmol) to a solution of 2-bromo-4-chlorobenzyl alcohol (200 mg, 0.9 mmol) in dichloromethane (4 mL). Stir the resulting mixture for 2 h. Add diethyl ether (4 mL) and stir for 20-min. Decant the diethyl ether solution. Wash the remaining solids with diethyl ether twice. Combine the diethyl ether solutions and concentrate. Chromatograph on silica gel, eluting with 20:80 to 1:1 ethyl acetate:dichloromethane to give 2-bromo-4-chlorobenzaldehyde as a white solid (167 mg, 85%). Decant the diethyl ether solution Wash the remaining solids with diethyl ether twice concentrate Chromatograph on silica gel, eluting with 20:80 to 1:1 ethyl acetate

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

Procedure: Add pyridinium chlorochromate (432 mg, 2 mmol) to a solution of 2-bromo-4-chlorobenzyl alcohol (200 mg, 0.9 mmol) in dichloromethane (4 mL). Stir the resulting mixture for 2 h. Add diethyl ether (4 mL) and stir for 20-min. Decant the diethyl ether solution. Wash the remaining solids with diethyl ether twice. Combine the diethyl ether solutions and concentrate. Chromatograph on silica gel, eluting with 20:80 to 1:1 ethyl acetate:dichloromethane to give 2-bromo-4-chlorobenzaldehyde as a white solid (167 mg, 85%). Decant the diethyl ether solution Wash the remaining solids with diethyl ether twice concentrate Chromatograph on silica gel, eluting with 20:80 to 1:1 ethyl acetate

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

Procedure: Add borane-THF (1 M in THF, 3.2 mL) complex dropwise to an ice-cooled solution of 2-bromo-4-chlorobenzoic acid (500 mg, 2.1 mmol) in THF (2 mL). Remove the cooling bath and stir overnight. Slowly add water (1 mL) and solid sodium carbonate. Stir 1 h. Filter and wash solids with THF. Chromatograph on silica gel, eluting with 0:100 to 30:70 ethyl acetate:dichloromethane to give 2-bromo-4-chlorobenzyl alcohol as a white solid (378 mg, 80%). Remove the cooling bath Stir 1 h Filter wash solids with THF Chromatograph on silica gel, eluting with 0:100 to 30:70 ethyl acetate

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

Procedure: Add borane-THF (1 M in THF, 3.2 mL) complex dropwise to an ice-cooled solution of 2-bromo-4-chlorobenzoic acid (500 mg, 2.1 mmol) in THF (2 mL). Remove the cooling bath and stir overnight. Slowly add water (1 mL) and solid sodium carbonate. Stir 1 h. Filter and wash solids with THF. Chromatograph on silica gel, eluting with 0:100 to 30:70 ethyl acetate:dichloromethane to give 2-bromo-4-chlorobenzyl alcohol as a white solid (378 mg, 80%). Remove the cooling bath Stir 1 h Filter wash solids with THF Chromatograph on silica gel, eluting with 0:100 to 30:70 ethyl acetate

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

Procedure: A solution of 2-bromo-4-chlorobenzaldehyde (21.95 g; 100.0 mmol) in 200 mL methanol was stirred and cooled in an ice bath for 15 minutes, and solid sodium borohydride (1.9 g; 50.0 mmol) was added. A yellow color formed and there was copious gas evolution. Stirring was continued in the bath for 1 hour. The solution was diluted with 200 mL water, and then the methanol was evaporated on a rotary evaporator. The residual mixture was extracted with 200 mL EtOAc. The organic layer was washed with 50 mL brine, then dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, ground with a mortar and pestle to break up the chunks, then washed with hexane and air-dried on the filter to give 17.8 g of (2-bromo-4-chlorophenyl)methanol as a white solid. cooled in an ice bath for 15 minutes A yellow color formed the methanol was evaporated on a rotary evaporator The residual mixture was extracted with 200 mL EtOAc The organic layer was washed with 50 mL brine dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration, ground with a mortar and pestle washed with hexane air-dried on the filter

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

Procedure: A solution of 2-bromo-4-chlorobenzaldehyde (21.95 g; 100.0 mmol) in 200 mL methanol was stirred and cooled in an ice bath for 15 minutes, and solid sodium borohydride (1.9 g; 50.0 mmol) was added. A yellow color formed and there was copious gas evolution. Stirring was continued in the bath for 1 hour. The solution was diluted with 200 mL water, and then the methanol was evaporated on a rotary evaporator. The residual mixture was extracted with 200 mL EtOAc. The organic layer was washed with 50 mL brine, then dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, ground with a mortar and pestle to break up the chunks, then washed with hexane and air-dried on the filter to give 17.8 g of (2-bromo-4-chlorophenyl)methanol as a white solid. cooled in an ice bath for 15 minutes A yellow color formed the methanol was evaporated on a rotary evaporator The residual mixture was extracted with 200 mL EtOAc The organic layer was washed with 50 mL brine dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration, ground with a mortar and pestle washed with hexane air-dried on the filter

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

Procedure: The title compound was prepared from (2-bromo-4-chlorophenyl)methanol and 4-fluoro-1-vinylbenzene according to the procedure for the preparation of Example 119, part B. 1H NMR (400 MHz, CDCl3): δ 1.72 (1H, t, J=5.6 Hz), 4.77 (2H, d, J=5.2 Hz), 6.98-7.08 (3H, m), 7.22-7.34 (3H, m), 7.47-7.50 (2H, m), 7.60 (1H, d, J=1.6 Hz).

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

Procedure: Added BH3 (1M in THF, 40 mL) to a solution of 2-bromo-4-chlorobenzoic acid (3.14 g, 13.33 mmol) in THF (3 mL) drop wise at 0° C. The reaction mixture was stirred at room temperature overnight. Extracted with ethyl acetate twice, and washed the organic phase with brine and dried with anhydrous Na2SO4, concentrated to give the title compound (2.5 g, 85%). Extracted with ethyl acetate twice washed the organic phase with brine dried with anhydrous Na2SO4 concentrated