(1R)-1-(2-fluorophenyl)ethanol

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

Procedure: 5-(4-Bromo-3-methyl-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1.78 g, 6.0 mmol) was dissolved in toluene (50 mL). Triethylamine (0.92 mL, 6.6 mmol) was added, followed by diphenylphosphoryl azide (1.43 mL, 6.6 mmol), and the mixture was stirred for 10 minutes. (R)-1-(2-Fluoro-phenyl)-ethanol (0.924 g, 6.6 mmol) was added, and the reaction was stirred at 85° C. for 3 hours, and then overnight at room temperature. The mixture was concentrated, and the residue was diluted with dichloromethane and purified by silica gel chromatography to give the title compound. the reaction was stirred at 85° C. for 3 hours overnight at room temperature The mixture was concentrated the residue was diluted with dichloromethane purified by silica gel chromatography

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

Procedure: 5-(4-Bromo-3-methyl-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1.78 g, 6.0 mmol) was dissolved in toluene (50 mL). Triethylamine (0.92 mL, 6.6 mmol) was added, followed by diphenylphosphoryl azide (1.43 mL, 6.6 mmol), and the mixture was stirred for 10 minutes. (R)-1-(2-Fluoro-phenyl)-ethanol (0.924 g, 6.6 mmol) was added, and the reaction was stirred at 85° C. for 3 hours, and then overnight at room temperature. The mixture was concentrated, and the residue was diluted with dichloromethane and purified by silica gel chromatography to give the title compound. the reaction was stirred at 85° C. for 3 hours overnight at room temperature The mixture was concentrated the residue was diluted with dichloromethane purified by silica gel chromatography

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

Procedure: 2′-Fluoroacetophenone (25 g, 180 mmol) and (S)-(−)-2-methyl-CBS-oxazaborolidine (6.02 g, 22 mmol) were combined in THF (200 mL). Borane methyl sulfide complex (2M in THF; 59.4 mL, 119 mmol) was added over 20 minutes, and the reaction was stirred at room temperature for 30 minutes. Methanol was added, and the mixture was worked-up with dichloromethane and water. The organic layer was concentrated to give (R)-1-(2-fluoro-phenyl)-ethanol in 90.6% e.e. The organic layer was concentrated

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

Procedure: 5-(4-Bromo-3-methyl-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1.78 g, 6.0 mmol) was dissolved in toluene (50 mL). Triethylamine (0.92 mL, 6.6 mmol) was added, followed by diphenylphosphoryl azide (1.43 mL, 6.6 mmol), and the mixture was stirred for 10 minutes. (R)-1-(2-Fluoro-phenyl)-ethanol (0.924 g, 6.6 mmol) was added, and the reaction was stirred at 85° C. for 3 hours, and then overnight at room temperature. The mixture was concentrated, and the residue was diluted with dichloromethane and purified by silica gel chromatography to give the title compound. the reaction was stirred at 85° C. for 3 hours overnight at room temperature The mixture was concentrated the residue was diluted with dichloromethane purified by silica gel chromatography

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

Procedure: 2′-Fluoroacetophenone (25 g, 180 mmol) and (S)-(−)-2-methyl-CBS-oxazaborolidine (6.02 g, 22 mmol) were combined in THF (200 mL). Borane methyl sulfide complex (2M in THF; 59.4 mL, 119 mmol) was added over 20 minutes, and the reaction was stirred at room temperature for 30 minutes. Methanol was added, and the mixture was worked-up with dichloromethane and water. The organic layer was concentrated to give (R)-1-(2-fluoro-phenyl)-ethanol in 90.6% e.e. The organic layer was concentrated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(4-bromophenyl)-5-methylisoxazole-4-carboxylic acid (0.100 g, 0.35 mmol) in toluene (3 mL) was added triethylamine (0.054 mL, 0.39 mmol) and diphenylphosphoryl azide (0.084 mL, 0.39 mmol), followed by (R)-1-(2-fluoro-phenyl)-ethanol (0.055 g, 0.39 mmol), and the reaction was stirred at 80° C. for 1 hour. Once no starting material was seen by analytical LCMS, standard aqueous work-up was performed. The organic layer was treated with silica gel, and the mixture was concentrated and purified by silica gel chromatography to give the title compound. The organic layer was treated with silica gel the mixture was concentrated purified by silica gel chromatography

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

Procedure: 2′-Fluoroacetophenone (25 g, 180 mmol) and (S)-(−)-2-methyl-CBS-oxazaborolidine (6.02 g, 22 mmol) were combined in THF (200 mL). Borane methyl sulfide complex (2M in THF; 59.4 mL, 119 mmol) was added over 20 minutes, and the reaction was stirred at room temperature for 30 minutes. MeOH was added, and the mixture was worked-up with CH2Cl2 and H2O. The organic layer was concentrated to give the title compound in 90.6% e.e., determined by HPLC analysis of the acetate derivative (made by reacting the benzyl alcohol with acetyl chloride and triethylamine in methylene chloride) using Chiralcel OD eluted with 99.8:0.2 Hexanes:EtOH; R isomer retention time 5.9 minutes. The organic layer was concentrated

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

Procedure: 5-(4-Bromo-3-methyl-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1.78 g, 6.0 mmol) was dissolved in toluene (50 mL). Triethylamine (0.92 mL, 6.6 mmol) was added, followed by diphenylphosphoryl azide (1.43 mL, 6.6 mmol), and the mixture was stirred for 10 minutes. (R)-1-(2-Fluoro-phenyl)-ethanol (0.924 g, 6.6 mmol) was added, and the reaction was stirred at 85° C. for 3 hours, and then overnight at room temperature. The mixture was concentrated, and the residue was diluted with dichloromethane and purified by silica gel chromatography to give the title compound. the reaction was stirred at 85° C. for 3 hours overnight at room temperature The mixture was concentrated the residue was diluted with dichloromethane purified by silica gel chromatography

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

Procedure: 2′-Fluoroacetophenone (25 g, 180 mmol) and (S)-(−)-2-methyl-CBS-oxazaborolidine (6.02 g, 22 mmol) were combined in THF (200 mL). Borane methyl sulfide complex (2M in THF; 59.4 mL, 119 mmol) was added over 20 minutes, and the reaction was stirred at room temperature for 30 minutes. Methanol was added, and the mixture was worked-up with dichloromethane and water. The organic layer was concentrated to give (R)-1-(2-fluoro-phenyl)-ethanol in 90.6% e.e. The organic layer was concentrated