1-amino-1-(3,4-difluorophenyl)propan-2-ol

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

Procedure: Recovery Procedure B. Cesium carbonate (2 g) was added to another portion of the hydroxy carbamate mixture, and after about thirty minutes at room temperature the reaction mixture was diluted with water (50 ml). Sulfuric acid (10 eq.) was then added, and the mixture was refluxed for 30 minutes to obtain a mixture of the title compound plus 1-(3,4-difluorophenyl)-2-hydroxy-propylamine. Isolation by neutralization with NaOH to a pH=8-9, and extraction with MTBE afforded the title compound, which was obtained in 90% ee by evaporative removal of the MTBE. the mixture was refluxed for 30 minutes to obtain

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

Procedure: To a well stirred solution of 1-(3,4-difluorophenyl)-2-hydroxy-propan-1-one-oxime (5.8 g, 28.4 mmol), was added a 1.0 M solution of LiAlH4 in ether (90 mL, 90 mmol) dropwise at 0° C. The resulting yellow solution was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C. and then carefully quenched sequentially with 3.5 mL of water, 3.5 mL of 3N NaOH followed by 10.5 mL of water. The resulting suspension was filtered thru a fritted glass funnel. To the residue was added 100 mL Et2O and the suspension was heated to reflux for 20 min. The suspension was filtered and was combined with the previous filtrate, dried over MgSO4, filtered and the solvent was removed in vacuo. 1-Amino-1-(3,4-difluorophenyl)-propan-2-ol was obtained as a yellow glassy syrup (3.6 g, 66%) which was used in the next step without further purification. The reaction mixture was cooled to 0° C. carefully quenched sequentially with 3.5 mL of water, 3.5 mL of 3N NaOH The resulting suspension was filtered To the residue was added 100 mL Et2O the suspension was heated to reflux for 20 min The suspension was filtered dried over MgSO4 filtered the solvent was removed in vacuo

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

Procedure: To a well stirred solution of 1-(3,4-difluorophenyl)-2-hydroxy-propan-1-one-oxime (5.8 g, 28.4 mmol), was added a 1.0 M solution of LiAlH4 in ether (90 mL, 90 mmol) dropwise at 0° C. The resulting yellow solution was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C. and then carefully quenched sequentially with 3.5 mL of water, 3.5 mL of 3N NaOH followed by 10.5 mL of water. The resulting suspension was filtered thro' a fritted glass funnel. To the residue was added 100 mL Et2O and the suspension was heated to reflux for 20 min. The suspension was filtered and was combined with the previous filtrate, dried over MgSO4, filtered and the solvent was removed in vacuo. 1-amino-1-(3,4-difluorophenyl)-propan-2-ol was obtained as a yellow glassy syrup (3.6 g, 66%) which was used in the next step without further purification. The reaction mixture was cooled to 0° C. carefully quenched sequentially with 3.5 mL of water, 3.5 mL of 3N NaOH The resulting suspension was filtered thro' a fritted glass funnel To the residue was added 100 mL Et2O the suspension was heated to reflux for 20 min The suspension was filtered dried over MgSO4 filtered the solvent was removed in vacuo

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

Procedure: To a well stirred solution of 1-(3,4-difluorophenyl)-2-hydroxy-propan-1-one-oxime (5.8 g, 28.4 mmol), was added a 1.0 M solution of LiAlH4 in ether (90 mL, 90 mmol) dropwise at 0° C. The resulting yellow solution was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C. and then carefully quenched sequentially with 3.5 mL of water, 3.5 mL of 3N NaOH followed by 10.5 mL of water. The resulting suspension was filtered thro′ a fritted glass funnel. To the residue was added 100 mL Et2O and the suspension was heated to reflux for 20 min. The suspension was filtered and was combined with the previous filtrate, dried over MgSO4, filtered and the solvent was removed in vacuo. 1-amino-1-(3,4-difluorophenyl)-propan-2-ol was obtained as a yellow glassy syrup (3.6 g, 66%) which was used in the next step without further purification. The reaction mixture was cooled to 0° C. carefully quenched sequentially with 3.5 mL of water, 3.5 mL of 3N NaOH The resulting suspension was filtered thro′ a fritted glass funnel To the residue was added 100 mL Et2O the suspension was heated to reflux for 20 min The suspension was filtered dried over MgSO4 filtered the solvent was removed in vacuo

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

Procedure: Recovery Procedure B. Cesium carbonate (2 g) was added to another portion of the hydroxy carbamate mixture, and after about thirty minutes at room temperature the reaction mixture was diluted with water (50 ml). Sulfuric acid (10 eq.) was then added, and the mixture was refluxed for 30 minutes to obtain a mixture of the title compound plus 1-(3,4-difluorophenyl)-2-hydroxy-propylamine. Isolation by neutralization with NaOH to a pH=8-9, and extraction with MTBE afforded the title compound, which was obtained in 90% ee by evaporative removal of the MTBE. the mixture was refluxed for 30 minutes to obtain