1-(5-bromo-2-chlorophenyl)ethanol

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

Procedure: Bis(2-methoxyethyl)aminosulfur trifluoride (4.5 g, 20.34 mmol) was added to a stirred solution of 1-(5-bromo-2-chlorophenyl)ethanol (3.99 g, 16.95 mmol) in dichloromethane (50 mL) at 0° C. The resulting solution was stirred at 0° C. for 3 h. The reaction mixture was quenched with a 5% solution of aqueous sodium bicarbonate (100 mL) and the resulting bubbling biphasic reaction mixture was vigorously stirred at 0° C. for 15 min. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane twice. The combined organic layers were washed with 1M hydrochloric acid, dried and concentrated by rotary evaporation. The product was purified by flash chromatography on silica gel (hexanes) to yield the title compound (2.65 g, 11.16 mmol, 65.8% yield) as a clear oil: 1H NMR (CDCl3) δ 7.65 (d, 1H), 7.37 (m, 1H), 7.20 (m, 1H), 5.88 (dq, 1H), 1.61 (dd, 3H). The reaction mixture was quenched with a 5% solution of aqueous sodium bicarbonate (100 mL) the resulting bubbling biphasic reaction mixture was vigorously stirred at 0° C. for 15 min extracted with dichloromethane twice The combined organic layers were washed with 1M hydrochloric acid dried concentrated by rotary evaporation The product was purified by flash chromatography on silica gel (hexanes)

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

Procedure: Bis(2-methoxyethyl)aminosulfur trifluoride (4.5 g, 20.34 mmol) was added to a stirred solution of 1-(5-bromo-2-chlorophenyl)ethanol (3.99 g, 16.95 mmol) in dichloromethane (50 mL) at 0° C. The resulting solution was stirred at 0° C. for 3 h. The reaction mixture was quenched with a 5% solution of aqueous sodium bicarbonate (100 mL) and the resulting bubbling biphasic reaction mixture was vigorously stirred at 0° C. for 15 min. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane twice. The combined organic layers were washed with 1M hydrochloric acid, dried and concentrated by rotary evaporation. The product was purified by flash chromatography on silica gel (hexanes) to yield the title compound (2.65 g, 11.16 mmol, 65.8% yield) as a clear oil: 1H NMR (CDCl3) δ 7.65 (d, 1H), 7.37 (m, 1H), 7.20 (m, 1H), 5.88 (dq, 1H), 1.61 (dd, 3H). The reaction mixture was quenched with a 5% solution of aqueous sodium bicarbonate (100 mL) the resulting bubbling biphasic reaction mixture was vigorously stirred at 0° C. for 15 min extracted with dichloromethane twice The combined organic layers were washed with 1M hydrochloric acid dried concentrated by rotary evaporation The product was purified by flash chromatography on silica gel (hexanes)

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

Procedure: Sodium borohydride (1.182 g, 51.4 mmol) was added to a stirred solution of 1-(5-bromo-2-chlorophenyl)ethanone (10 g, 42.8 mmol) in methanol at 0° C. The resulting bubbling white mixture was allowed to warm to ambient temperature and stirred for 2 h. The reaction mixture was quenched with acetone (50 mL) and concentrated by rotary evaporation. The residue was partitioned between ethyl acetate and water. The organic phase was dried and concentrated to yield the title compound (10 g, 99% yield) as a white solid: 1H NMR (CDCl3) δ 7.75 (d, 1H), 7.32 (m, 1H), 7.19 (m, 1H), 5.23 (q, 1H), 1.95 (d, 1H), 1.48 (d, 3H). The resulting bubbling white mixture The reaction mixture was quenched with acetone (50 mL) concentrated by rotary evaporation The residue was partitioned between ethyl acetate and water The organic phase was dried concentrated

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

Procedure: Sodium borohydride (1.182 g, 51.4 mmol) was added to a stirred solution of 1-(5-bromo-2-chlorophenyl)ethanone (10 g, 42.8 mmol) in methanol at 0° C. The resulting bubbling white mixture was allowed to warm to ambient temperature and stirred for 2 h. The reaction mixture was quenched with acetone (50 mL) and concentrated by rotary evaporation. The residue was partitioned between ethyl acetate and water. The organic phase was dried and concentrated to yield the title compound (10 g, 99% yield) as a white solid: 1H NMR (CDCl3) δ 7.75 (d, 1H), 7.32 (m, 1H), 7.19 (m, 1H), 5.23 (q, 1H), 1.95 (d, 1H), 1.48 (d, 3H). The resulting bubbling white mixture The reaction mixture was quenched with acetone (50 mL) concentrated by rotary evaporation The residue was partitioned between ethyl acetate and water The organic phase was dried concentrated

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

Procedure: Methyl lithium (11.6 mL, 16.3 mmol, 1.4M in ether) was added to a cooled −78° C. solution of 5-bromo-2-chloro-benzaldehyde (2.75 g, 12.5 mmol) dissolved in THF (40 mL). The reaction mixture was stirred for 15 hours and then quenched with saturated NH4Cl and extracted with EtOAc. The organic extracts were washed with 1N HCl, brine, dried over Na2SO4 and concentrated to an oil. The oil was purified by flash column chromatography (0% to 10% EtOAc in hexanes) to give the title compound as a solid (2.63 g, 91%). 1H NMR (400 MHz, CDCl3): δ 6.32 (d, J=6.3 Hz, 3 H), 2.00 (d, J=3.8 Hz, 1 H), 5.24 (m, 1 H), 7.19 (d, J=8.6 Hz, 1 H), 7.33 (dd, J=8.6, 2.5 Hz, 1 H), 7.75 (d, J=2.5 Hz, 1 H). quenched with saturated NH4Cl extracted with EtOAc The organic extracts were washed with 1N HCl, brine dried over Na2SO4 concentrated to an oil The oil was purified by flash column chromatography (0% to 10% EtOAc in hexanes)

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

Procedure: Pyridinium dichromate (2.6 g, 6.94 mmol) was added to a solution of 1-(5-bromo-2-chloro-phenyl)-ethanol (1.09 g, 4.6 mmol) in CH2Cl2 (20 mL). The reaction was stirred for 15 hours and then more pyridinium dichromate (2.6 g, 6.94 mmol) was added. After another 24 hours celite was added and the mixture was stirred for 20 mins. The reaction mixture was filtered through a pad of celite washing with ether. The filtrate was concentrated to a brown oil. The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes) to give the title compound as a clear oil (0.92 g, 85%). 1H NMR (400 MHz, CDCl3): δ 2.64 (s, 3H), 7.29 (d, J=8.6 Hz, 1 H), 7.51 (dd, J=8.6, 2.3 Hz, 1 H), 7.66 (d, J=2.3 Hz, 1 H). After another 24 hours celite was added the mixture was stirred for 20 mins The reaction mixture was filtered through a pad of celite washing with ether The filtrate was concentrated to a brown oil The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes)

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

Procedure: Pyridinium dichromate (2.6 g, 6.94 mmol) was added to a solution of 1-(5-bromo-2-chloro-phenyl)-ethanol (1.09 g, 4.6 mmol) in CH2Cl2 (20 mL). The reaction was stirred for 15 hours and then more pyridinium dichromate (2.6 g, 6.94 mmol) was added. After another 24 hours celite was added and the mixture was stirred for 20 mins. The reaction mixture was filtered through a pad of celite washing with ether. The filtrate was concentrated to a brown oil. The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes) to give the title compound as a clear oil (0.92 g, 85%). 1H NMR (400 MHz, CDCl3): δ 2.64 (s, 3H), 7.29 (d, J=8.6 Hz, 1 H), 7.51 (dd, J=8.6, 2.3 Hz, 1 H), 7.66 (d, J=2.3 Hz, 1 H). After another 24 hours celite was added the mixture was stirred for 20 mins The reaction mixture was filtered through a pad of celite washing with ether The filtrate was concentrated to a brown oil The residue was purified by flash silica gel chromatography (0% to 10% EtOAc in hexanes)

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

Procedure: Bis(2-methoxyethyl)aminosulfur trifluoride (4.5 g, 20.34 mmol) was added to a stirred solution of 1-(5-bromo-2-chlorophenyl)ethanol (3.99 g, 16.95 mmol) in dichloromethane (50 mL) at 0° C. The resulting solution was stirred at 0° C. for 3 h. The reaction mixture was quenched with a 5% solution of aqueous sodium bicarbonate (100 mL) and the resulting bubbling biphasic reaction mixture was vigorously stirred at 0° C. for 15 min. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane twice. The combined organic layers were washed with 1M hydrochloric acid, dried and concentrated by rotary evaporation. The product was purified by flash chromatography on silica gel (hexanes) to yield the title compound (2.65 g, 11.16 mmol, 65.8% yield) as a clear oil: 1H NMR (CDCl3) δ 7.65 (d, 1H), 7.37 (m, 1H), 7.20 (m, 1H), 5.88 (dq, 1H), 1.61 (dd, 3H). The reaction mixture was quenched with a 5% solution of aqueous sodium bicarbonate (100 mL) the resulting bubbling biphasic reaction mixture was vigorously stirred at 0° C. for 15 min extracted with dichloromethane twice The combined organic layers were washed with 1M hydrochloric acid dried concentrated by rotary evaporation The product was purified by flash chromatography on silica gel (hexanes)

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

Procedure: Sodium borohydride (1.182 g, 51.4 mmol) was added to a stirred solution of 1-(5-bromo-2-chlorophenyl)ethanone (10 g, 42.8 mmol) in methanol at 0° C. The resulting bubbling white mixture was allowed to warm to ambient temperature and stirred for 2 h. The reaction mixture was quenched with acetone (50 mL) and concentrated by rotary evaporation. The residue was partitioned between ethyl acetate and water. The organic phase was dried and concentrated to yield the title compound (10 g, 99% yield) as a white solid: 1H NMR (CDCl3) δ 7.75 (d, 1H), 7.32 (m, 1H), 7.19 (m, 1H), 5.23 (q, 1H), 1.95 (d, 1H), 1.48 (d, 3H). The resulting bubbling white mixture The reaction mixture was quenched with acetone (50 mL) concentrated by rotary evaporation The residue was partitioned between ethyl acetate and water The organic phase was dried concentrated