1-benzyl-3,3-difluoropiperidin-4-ol

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 1-benzyl-3,3-difluoropiperidine-4,4-diol (WO2008/121687 and WO2005/040120) (2.88 g, 11.85 mmol) in dry MeOH (58 mL) was added NaBH4 (672 mg, 17.76 mmol) portionwise at 0° C. The reaction mixture was stirred at 0° C. for 15 min. Aq. 0.1M NaHCO3 (5 mL) was then added and the mixture further stirred for 5 min, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA, 2:1→1:1) and the title compound obtained as a beige oil. LC-MS-conditions 08: tR=0.42 min; [M+H]+=228.32. the mixture further stirred for 5 min dried (MgSO4) filtered concentrated under reduced pressure The crude residue was purified by FC (hept-EA, 2:1→1:1)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 1-benzyl-3,3-difluoropiperidine-4,4-diol (WO2008/121687 and WO2005/040120) (2.88 g, 11.85 mmol) in dry MeOH (58 mL) was added NaBH4 (672 mg, 17.76 mmol) portionwise at 0° C. The reaction mixture was stirred at 0° C. for 15 min. Aq. 0.1M NaHCO3 (5 mL) was then added and the mixture further stirred for 5 min, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA, 2:1→1:1) and the title compound obtained as a beige oil. LC-MS-conditions 08: tR=0.42 min; [M+H]+=228.32. the mixture further stirred for 5 min dried (MgSO4) filtered concentrated under reduced pressure The crude residue was purified by FC (hept-EA, 2:1→1:1)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar, a suspension of 1-benzyl-3,3-difluoropiperidin-4-ol (1.73 g, 7.62 mmol) and Pd(OH)2 (20% Pd, 107 mg) in dry EtOH (50 mL) was stirred at rt under a H2 atmospheric pressure until completion of the reaction. The mixture was then filtered, washed with EA/EtOH, and the filtrate concentrated under reduced pressure to give the title compound as a beige solid. In a flame dried round-bottomed flask equipped with a magnetic stir bar until completion of the reaction The mixture was then filtered washed with EA/EtOH the filtrate concentrated under reduced pressure

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar, a suspension of 1-benzyl-3,3-difluoropiperidin-4-ol (1.73 g, 7.62 mmol) and Pd(OH)2 (20% Pd, 107 mg) in dry EtOH (50 mL) was stirred at rt under a H2 atmospheric pressure until completion of the reaction. The mixture was then filtered, washed with EA/EtOH, and the filtrate concentrated under reduced pressure to give the title compound as a beige solid. LC-MS-conditions 08: tR=0.15 min; [M+H]+=138.27. In a flame dried round-bottomed flask equipped with a magnetic stir bar until completion of the reaction The mixture was then filtered washed with EA/EtOH the filtrate concentrated under reduced pressure

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 1-benzyl-3,3-difluoropiperidine-4,4-diol (WO2008/121687 and WO2005/040120) (2.88 g, 11.85 mmol) in dry MeOH (58 mL) was added NaBH4 (672 mg, 17.76 mmol) portionwise at 0° C. The reaction mixture was stirred at 0° C. for 15 min. Aq. 0.1M NaHCO3 (5 mL) was then added and the mixture further stirred for 5 min, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept/EA, 2:1→1:1) and the title compound obtained as a beige oil. LC-MS-conditions 08: tR=0.42 min; [M+H]+=228.32. the mixture further stirred for 5 min dried (MgSO4) filtered concentrated under reduced pressure The crude residue was purified by FC (hept/EA, 2:1→1:1)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 1-benzyl-3,3-difluoropiperidine-4,4-diol (WO2008/121687 and WO2005/040120) (2.88 g, 11.85 mmol) in dry MeOH (58 mL) was added NaBH4 (672 mg, 17.76 mmol) portionwise at 0° C. The reaction mixture was stirred at 0° C. for 15 min. Aq. 0.1M NaHCO3 (5 mL) was then added and the mixture further stirred for 5 min, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept/EA, 2:1→1:1) and the title compound obtained as a beige oil. LC-MS-conditions 08: tR=0.42 min; [M+H]+=228.32. the mixture further stirred for 5 min dried (MgSO4) filtered concentrated under reduced pressure The crude residue was purified by FC (hept/EA, 2:1→1:1)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 1-benzyl-3,3-difluoropiperidine-4,4-diol (WO2008/121687 and WO2005/040120) (2.88 g, 11.85 mmol) in dry MeOH (58 mL) was added NaBH4 (672 mg, 17.76 mmol) portionwise at 0° C. The reaction mixture was stirred at 0° C. for 15 min. Aq. 0.1M NaHCO3 (5 mL) was then added and the mixture further stirred for 5 min, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept/EA, 2:1→1:1) and the title compound obtained as a beige oil. LC-MS-conditions 08: tR=0.42 min; [M+H]+=228.32. the mixture further stirred for 5 min dried (MgSO4) filtered concentrated under reduced pressure The crude residue was purified by FC (hept/EA, 2:1→1:1)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 1-benzyl-3,3-difluoropiperidine-4,4-diol (WO2008/121687 and WO2005/040120) (2.88 g, 11.85 mmol) in dry MeOH (58 mL) was added NaBH4 (672 mg, 17.76 mmol) portionwise at 0° C. The reaction mixture was stirred at 0° C. for 15 min. Aq. 0.1M NaHCO3 (5 mL) was then added and the mixture further stirred for 5 min, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA, 2:1→1:1) and the title compound obtained as a beige oil. LC-MS-conditions 08: tR=0.42 min; [M+H]+=228.32. the mixture further stirred for 5 min dried (MgSO4) filtered concentrated under reduced pressure The crude residue was purified by FC (hept-EA, 2:1→1:1)

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

Procedure: In a flame dried round-bottomed flask equipped with a magnetic stir bar, a suspension of 1-benzyl-3,3-difluoropiperidin-4-ol (1.73 g, 7.62 mmol) and Pd(OH)2 (20% Pd, 107 mg) in dry EtOH (50 mL) was stirred at rt under a H2 atmospheric pressure until completion of the reaction. The mixture was then filtered, washed with EA/EtOH, and the filtrate concentrated under reduced pressure to give the title compound as a beige solid. In a flame dried round-bottomed flask equipped with a magnetic stir bar until completion of the reaction The mixture was then filtered washed with EA/EtOH the filtrate concentrated under reduced pressure