(1S)-2-bromo-1-(4-bromophenyl)ethanol

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

Procedure: Aqueous sodium hydroxide (1M, 400 ml) was added to 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77.0 g) in diethyl ether (400 ml) and stirred at room temperature for 5 hours. The organic layer was separated and water layer was extracted with ether. Combined organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent yielded (2S)-2-(4-bromophenyl)oxirane (55.0 g) as a pale brown oil. The organic layer was separated water layer was extracted with ether Combined organic layer was washed with brine dried over anhydrous sodium sulfate Removal of the solvent

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

Procedure: A borane-tetrahydrofuran complex (1.0 M solution in tetrahydrofuran, 270 ml, 270 mmol) was added to the solution of (S)-CBS ((S)-2-Methyl-CBS-oxazaborolidine, 50 ml, 1.0M solution in toluene) at −30° C. over 15 min and the solution was stirred for 15 minutes. 4-Bromophenacyl bromide (75.0 g, 270 mmol) in dichloromethane (350 ml) was dropped over 70 minutes keeping the temperature −32 to −28° C. After one hour stirring, solution was warmed to room temperature, and methanol (10 ml) was added slowly and then 0.5 M hydrochloric acid (300 ml) was dropped over 10 minutes. The solution was filtered after 40 minutes stirring and filtrate was extracted by dichloromethane. The combined organic layer was washed with 0.5 M hydrochloric acid, 0.1M aqueous sodium hydroxide and brine and dried over anhydrous sodium sulfate. Concentration of the organic layer yielded 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77 g) as a pale brown oil. the temperature −32 to −28° C After one hour stirring The solution was filtered after 40 minutes stirring filtrate was extracted by dichloromethane The combined organic layer was washed with 0.5 M hydrochloric acid, 0.1M aqueous sodium hydroxide and brine dried over anhydrous sodium sulfate

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

Procedure: Aqueous sodium hydroxide (1M, 400 ml) was added to 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77.0 g) in diethyl ether (400 ml) and stirred at room temperature for 5 hours. The organic layer was separated and aqueous layer was extracted with ether. The combined organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent yielded (2S)-2-(4-bromophenyl) oxirane (55.0 g) as a pale brown oil. The organic layer was separated aqueous layer was extracted with ether The combined organic layer was washed with brine dried over anhydrous sodium sulfate Removal of the solvent

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

Procedure: A borane-tetrahydrofuran complex (1.0 M solution in tetrahydrofuran, 270 ml, 270 mmol) was added to the solution of (S)—CBS ((S)-2-methyl-CBS-oxazaborolidine, 50 ml, 1.0M solution in toluene) at −30° C. over 15 minutes and the solution was stirred for 15 minutes. 4-Bromophenacyl bromide (75.0 g, 270 mmol) in dichloromethane (350 ml) was dropped over 70 minutes keeping the temperature −32 to −28° C. After one hour stirring, the solution was warmed to room temperature, and methanol (10 ml) was added slowly and then 0.5 M hydrochloric acid (300 ml) was dropped over 10 minutes. The solution was filtered after 40 minutes stirring and filtrate was extracted with dichloromethane. The combined organic layer was washed with 0.5 M hydrochloric acid, 0.1M aqueous sodium hydroxide and brine and dried over anhydrous sodium sulfate. Concentration of the organic layer yielded 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77 g) as a pale brown oil. the temperature −32 to −28° C After one hour stirring The solution was filtered after 40 minutes stirring filtrate was extracted with dichloromethane The combined organic layer was washed with 0.5 M hydrochloric acid, 0.1M aqueous sodium hydroxide and brine dried over anhydrous sodium sulfate

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

Procedure: Aqueous sodium hydroxide (1M, 400 ml) was added to 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77.0 g) in diethyl ether (400 ml) and stirred at room temperature for 5 hours. The organic layer was separated and water layer was extracted with ether. Combined organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent yielded (2S)-2-(4-bromophenyl)oxirane (55.0 g) as a pale brown oil. The organic layer was separated water layer was extracted with ether Combined organic layer was washed with brine dried over anhydrous sodium sulfate Removal of the solvent

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

Procedure: Aqueous sodium hydroxide (1M, 400 ml) was added to 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77.0 g) in diethyl ether (400 ml) and stirred at room temperature for 5 hours. The organic layer was separated and water layer was extracted with ether. Combined organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent yielded (2S)-2-(4-bromophenyl)oxirane (55.0 g) as a pale brown oil. The organic layer was separated water layer was extracted with ether Combined organic layer was washed with brine dried over anhydrous sodium sulfate Removal of the solvent

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

Procedure: A borane-tetrahydrofuran complex (1.0 M solution in tetrahydrofuran, 270 ml, 270 mmol) was added to the solution of (S)-CBS ((S)-2-Methyl-CBS-oxazaborolidine, 50 ml, 1.0M solution in toluene) at −30° C. over 15 min and the solution was stirred for 15 minutes. 4-Bromophenacyl bromide (75.0 g, 270 mmol) in dichloromethane (350 ml) was dropped over 70 minutes keeping the temperature −32 to −28° C. After one hour stirring, solution was warmed to room temperature, and methanol (10 ml) was added slowly and then 0.5 M hydrochloric acid (300 ml) was dropped over 10 minutes. The solution was filtered after 40 minutes stirring and filtrate was extracted by dichloromethane. The combined organic layer was washed with 0.5 M hydrochloric acid, 0.1M aqueous sodium hydroxide and brine and dried over anhydrous sodium sulfate. Concentration of the organic layer yielded 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77 g) as a pale brown oil. the temperature −32 to −28° C After one hour stirring The solution was filtered after 40 minutes stirring filtrate was extracted by dichloromethane The combined organic layer was washed with 0.5 M hydrochloric acid, 0.1M aqueous sodium hydroxide and brine dried over anhydrous sodium sulfate

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

Procedure: (S)—CBS (25 ml, (S)-2-methyl-CBS-oxazaborolidine, manufactured by Aldrich, 1.0 M solution in toluene) was cooled to 0° C., and borane-tetrahydrofuran complex (185 ml, 185 mmol, 1.0 M solution in tetrahydrofuran) was added. After the flask was cooled by ice-sodium chloride bath, a solution of 4-bromophenacyl bromide (intermediate 8, 50. 28 g, 181 mmol) in dichloromethane (300 ml) was added dropwise over one hour while maintaining the temperature at −5° C. to 0° C. After stirring the mixture at 0° C. for 50 minutes, methanol (12 ml) was added by small portions. Then, 0.5 M hydrochloric acid (300 ml) was added dropwise and the mixture was stirred at room temperature for 40 minutes. The precipitate was filtered off and the filtrate was partitioned between dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined, washed twice with 0.5 M hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford 2-bromo-1-(1S)-(4-bromophenyl)ethanol (intermediate 9) as a pale-brown oil. This crude product was used for next step without purification. After the flask was cooled by ice-sodium chloride bath while maintaining the temperature at −5° C. to 0° C the mixture was stirred at room temperature for 40 minutes The precipitate was filtered off the filtrate was partitioned between dichloromethane and water The organic layer was separated the aqueous layer was extracted with methylene chloride washed twice with 0.5 M hydrochloric acid and brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

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

Procedure: (S)—CBS (25 ml, (S)-2-methyl-CBS-oxazaborolidine, manufactured by Aldrich, 1.0 M solution in toluene) was cooled to 0° C., and borane-tetrahydrofuran complex (185 ml, 185 mmol, 1.0 M solution in tetrahydrofuran) was added. After the flask was cooled by ice-sodium chloride bath, a solution of 4-bromophenacyl bromide (intermediate 8, 50. 28 g, 181 mmol) in dichloromethane (300 ml) was added dropwise over one hour while maintaining the temperature at −5° C. to 0° C. After stirring the mixture at 0° C. for 50 minutes, methanol (12 ml) was added by small portions. Then, 0.5 M hydrochloric acid (300 ml) was added dropwise and the mixture was stirred at room temperature for 40 minutes. The precipitate was filtered off and the filtrate was partitioned between dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined, washed twice with 0.5 M hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford 2-bromo-1-(1S)-(4-bromophenyl)ethanol (intermediate 9) as a pale-brown oil. This crude product was used for next step without purification. After the flask was cooled by ice-sodium chloride bath while maintaining the temperature at −5° C. to 0° C the mixture was stirred at room temperature for 40 minutes The precipitate was filtered off the filtrate was partitioned between dichloromethane and water The organic layer was separated the aqueous layer was extracted with methylene chloride washed twice with 0.5 M hydrochloric acid and brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

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

Procedure: (S)-CBS (25 ml, (S)-2-methyl-CBS-oxazaborolidine, manufactured by Aldrich, 1.0 M solution in toluene) was cooled to 0° C., and borane-tetrahydrofuran complex (185 ml, 185 mmol, 1.0 M solution in tetrahydrofuran) was added. After the flask was cooled by ice-sodium chloride bath, a solution of 4-bromophenacyl bromide (intermediate 8, 50.28 g, 181 mmol) in dichloromethane (300 ml) was added dropwise over one hour while maintaining the temperature at −5° C. to 0° C. After stirring the mixture at 0° C. for 50 minutes, methanol (12 ml) was added by small portions. Then, 0.5 M hydrochloric acid (300 ml) was added dropwise and the mixture was stirred at room temperature for 40 minutes. The precipitate was filtered off and the filtrate was partitioned between dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined, washed twice with 0.5 M hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford 2-bromo-1-(1S)-(4-bromophenyl)ethanol (intermediate 9) as a pale-brown oil. This crude product was used for next step without purification. After the flask was cooled by ice-sodium chloride bath while maintaining the temperature at −5° C. to 0° C the mixture was stirred at room temperature for 40 minutes The precipitate was filtered off the filtrate was partitioned between dichloromethane and water The organic layer was separated the aqueous layer was extracted with methylene chloride washed twice with 0.5 M hydrochloric acid and brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

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

Procedure: (S)-CBS (25 ml, (S)-2-methyl-CBS-oxazaborolidine, manufactured by Aldrich, 1.0 M solution in toluene) was cooled to 0° C., and borane-tetrahydrofuran complex (185 ml, 185 mmol, 1.0 M solution in tetrahydrofuran) was added. After the flask was cooled by ice-sodium chloride bath, a solution of 4-bromophenacyl bromide (intermediate 2, 50.28 g, 181 mmol) in dichloromethane (300 ml) was added dropwise over one hour while maintaining the temperature at −5° C. to 0° C. After stirring the mixture at 0° C. for 50 minutes, methanol (12 ml) was added by small portions. Then, 0.5 M hydrochloric acid (300 ml) was added dropwise and the mixture was stirred at room temperature for 40 minutes. The precipitate was filtered off and the filtrate was partitioned between dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined, washed twice with 0.5 M hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford 2-bromo-1-(1S)-(4-bromophenyl)ethanol (intermediate 3) as a pale-brown oil. This crude product was used for next step without purification. After the flask was cooled by ice-sodium chloride bath while maintaining the temperature at −5° C. to 0° C the mixture was stirred at room temperature for 40 minutes The precipitate was filtered off the filtrate was partitioned between dichloromethane and water The organic layer was separated the aqueous layer was extracted with methylene chloride washed twice with 0.5 M hydrochloric acid and brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

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

Procedure: (S)—CBS (25 ml, (S)-2-methyl-CBS-oxazaborolidine, manufactured by Aldrich, 1.0 M solution in toluene) was cooled to 0° C., and borane-tetrahydrofuran complex (185 ml, 185 mmol, 1.0 M solution in tetrahydrofuran) was added. After the flask was cooled by ice-sodium chloride bath, a solution of 4-bromophenacyl bromide (intermediate 8, 50. 28 g, 181 mmol) in dichloromethane (300 ml) was added dropwise over one hour while maintaining the temperature at −5° C. to 0° C. After stirring the mixture at 0° C. for 50 minutes, methanol (12 ml) was added by small portions. Then, 0.5 M hydrochloric acid (300 ml) was added dropwise and the mixture was stirred at room temperature for 40 minutes. The precipitate was filtered off and the filtrate was partitioned between dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined, washed twice with 0.5 M hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford 2-bromo-1-(1S)-(4-bromophenyl)ethanol (intermediate 9) as a pale-brown oil. This crude product was used for next step without purification. After the flask was cooled by ice-sodium chloride bath while maintaining the temperature at −5° C. to 0° C the mixture was stirred at room temperature for 40 minutes The precipitate was filtered off the filtrate was partitioned between dichloromethane and water The organic layer was separated the aqueous layer was extracted with methylene chloride washed twice with 0.5 M hydrochloric acid and brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure