(1R)-1-piperidin-4-ylethanol

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

Procedure: A solution of 3-(1-methylethyl)-5-(trichloromethyl)-1,2,4-oxadiazole (25.8 g, 112 mmol) and (1R)-1-(4-piperidinyl)ethanol (13.4 g, 104 mmol) in MeOH (15 mL) was stirred at ambient temperature under a stream of nitrogen for 7 days. The reaction was diluted with MeOH (40 mL), cooled in an ice bath and 1N NaOH (25 mL) was added. The mixture was allowed to warm to ambient temperature and stir for 1 h. The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) and the layers were separated. The aqueous layer was saturated with NaCl and extracted with EtOAc (200 mL). The combined EtOAc layers were dried over MgSO4, concentrated and placed under high vacuum for 18 h to afford (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethanol (16.75 g, 68%) as an orange oil. 1H NMR (400 MHz, CDCl3): δ 4.14 (m, 2H), 3.57 (quint, 1H, J=6.3 Hz), 2.98 (m, 2H), 2.83 (septet, 1H, J=7.0 Hz), 1.90 (m, 1H), 1.86 (br, 1H), 1.67 (m, 1H), 1.45 (m, 1H), 1.33 (m, 2H), 1.23 (d, 6H, J=7.0 Hz), 1.16 (d, 3H, J=6.3 Hz); LRMS (ESI), m/z 240 (M+H). cooled in an ice bath The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) the layers were separated extracted with EtOAc (200 mL) The combined EtOAc layers were dried over MgSO4 concentrated placed under high vacuum for 18 h

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

Procedure: A solution of (1R)-1-(4-pyridinyl)ethanol (37 g, 0.3 mol, 78% ee) in MeOH (2 L) was charged with PtO2 (5 g) under nitrogen atmosphere followed by acetic acid (19 mL). The mixture was evacuated and purged with hydrogen several times and then stirred under an atmosphere of hydrogen for 2 d at room temperature. The mixture was filtered to remove catalyst and the filtrate was concentrated in vacuo and triturated with EtOAc to yield a cream-colored solid which was collected by filtration. The filter cake was dissolved in MeOH (500 mL) and 50% NaOH (15.8 g) was added. The resulting solution was stirred at 25° C. for 30 min and concentrated. The resulting solid was triturated with Et2O (700 mL) and stirred at 25° C. for 30 min, the solids were removed by filtration and the filtrate was dried over MgSO4 and filtered again. The final filtrate was concentrated to yield (1R)-1-(4-piperidinyl)ethanol (22 g, 57% yield) as a light beige solid. 1H NMR (400 MHz, CDCl3): δ 3.50 (quint, 1H, J=6.3 Hz), 3.13-3.01 (m, 2H), 2.61-2.47 (m, 2H), 1.88 (br, 2H), 1.84-1.73 (m, 1H), 1.63-1.52 (m, 1H), 1.41-1.27 (m, 1H), 1.23-1.05 (m, 2H), 1.13 (d, 3H, J=6.2 Hz). The mixture was evacuated purged with hydrogen several times The mixture was filtered to remove catalyst the filtrate was concentrated in vacuo triturated with EtOAc to yield a cream-colored solid which was collected by filtration The filter cake was dissolved in MeOH (500 mL) 50% NaOH (15.8 g) was added The resulting solution was stirred at 25° C. for 30 min concentrated The resulting solid was triturated with Et2O (700 mL) stirred at 25° C. for 30 min the solids were removed by filtration the filtrate was dried over MgSO4 filtered again The final filtrate was concentrated

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

Procedure: A solution of 3-(1-methylethyl)-5-(trichloromethyl)-1,2,4-oxadiazole (25.8 g, 112 mmol) and (1R)-1-(4-piperidinyl)ethanol (13.4 g, 104 mmol) in MeOH (15 mL) was stirred at ambient temperature under a stream of nitrogen for 7 days. The reaction was diluted with MeOH (40 mL), cooled in an ice bath and 1N NaOH (25 mL) was added. The mixture was allowed to warm to ambient temperature and stir for 1 h. The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) and the layers were separated. The aqueous layer was saturated with NaCl and extracted with EtOAc (200 mL). The combined EtOAc layers were dried over MgSO4, concentrated and placed under high vacuum for 18 h to afford (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethanol (16.75 g, 68%) as an orange oil. 1H NMR (400 MHz, CDCl3): δ 4.14 (m, 2H), 3.57 (quint, 1H, J=6.3 Hz), 2.98 (m, 2H), 2.83 (septet, 1H, J=7.0 Hz), 1.90 (m, 1H), 1.86 (br, 1H), 1.67 (m, 1H), 1.45 (m, 1H), 1.33 (m, 2H), 1.23 (d, 6H, J=7.0 Hz), 1.16 (d, 3H, J=6.3 Hz); LRMS (ESI), m/z 240 (M+H). cooled in an ice bath The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) the layers were separated extracted with EtOAc (200 mL) The combined EtOAc layers were dried over MgSO4 concentrated placed under high vacuum for 18 h

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

Procedure: A solution of 3-(1-methylethyl)-5-(trichloromethyl)-1,2,4-oxadiazole (25.8 g, 112 mmol) and (1R)-1-(4-piperidinyl)ethanol (13.4 g, 104 mmol) in MeOH (15 mL) was stirred at ambient temperature under a stream of nitrogen for 7 days. The reaction was diluted with MeOH (40 mL), cooled in an ice bath and 1N NaOH (25 mL) was added. The mixture was allowed to warm to ambient temperature and stir for 1 h. The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) and the layers were separated. The aqueous layer was saturated with NaCl and extracted with EtOAc (200 mL). The combined EtOAc layers were dried over MgSO4, concentrated and placed under high vacuum for 18 h to afford (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethanol (16.75 g, 68%) as an orange oil. 1H NMR (400 MHz, CDCl3): δ 4.14 (m, 2H), 3.57 (quint, 1H, J=6.3 Hz), 2.98 (m, 2H), 2.83 (septet, 1H, J=7.0 Hz), 1.90 (m, 1H), 1.86 (br, 1H), 1.67 (m, 1H), 1.45 (m, 1H), 1.33 (m, 2H), 1.23 (d, 6H, J=7.0 Hz), 1.16 (d, 3H, J=6.3 Hz); LRMS (ESI), m/z 240 (M+H). cooled in an ice bath The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) the layers were separated extracted with EtOAc (200 mL) The combined EtOAc layers were dried over MgSO4 concentrated placed under high vacuum for 18 h

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

Procedure: A solution of (1R)-1-(4-pyridinyl)ethanol (37 g, 0.3 mol, 78% ee) in MeOH (2 L) was charged with PtO2 (5 g) under nitrogen atmosphere followed by acetic acid (19 mL). The mixture was evacuated and purged with hydrogen several times and then stirred under an atmosphere of hydrogen for 2 d at room temperature. The mixture was filtered to remove catalyst and the filtrate was concentrated in vacuo and triturated with EtOAc to yield a cream-colored solid which was collected by filtration. The filter cake was dissolved in MeOH (500 mL) and 50% NaOH (15.8 g) was added. The resulting solution was stirred at 25° C. for 30 min and concentrated. The resulting solid was triturated with Et2O (700 mL) and stirred at 25° C. for 30 min, the solids were removed by filtration and the filtrate was dried over MgSO4 and filtered again. The final filtrate was concentrated to yield (1R)-1-(4-piperidinyl)ethanol (22 g, 57% yield) as a light beige solid. 1H NMR (400 MHz, CDCl3): δ 3.50 (quint, 1H, J=6.3 Hz), 3.13-3.01 (m, 2H), 2.61-2.47 (m, 2H), 1.88 (br, 2H), 1.84-1.73 (m, 1H), 1.63-1.52 (m, 1H), 1.41-1.27 (m, 1H), 1.23-1.05 (m, 2H), 1.13 (d, 3H, J=6.2 Hz). The mixture was evacuated purged with hydrogen several times The mixture was filtered to remove catalyst the filtrate was concentrated in vacuo triturated with EtOAc to yield a cream-colored solid which was collected by filtration The filter cake was dissolved in MeOH (500 mL) 50% NaOH (15.8 g) was added The resulting solution was stirred at 25° C. for 30 min concentrated The resulting solid was triturated with Et2O (700 mL) stirred at 25° C. for 30 min the solids were removed by filtration the filtrate was dried over MgSO4 filtered again The final filtrate was concentrated

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

Procedure: A solution of (1R)-1-(4-pyridinyl)ethanol (37 g, 0.3 mol, 78% ee) in MeOH (2 L) was charged with PtO2 (5 g) under nitrogen atmosphere followed by acetic acid (19 mL). The mixture was evacuated and purged with hydrogen several times and then stirred under an atmosphere of hydrogen for 2 d at room temperature. The mixture was filtered to remove catalyst and the filtrate was concentrated in vacuo and triturated with EtOAc to yield a cream-colored solid which was collected by filtration. The filter cake was dissolved in MeOH (500 mL) and 50% NaOH (15.8 g) was added. The resulting solution was stirred at 25° C. for 30 min and concentrated. The resulting solid was triturated with Et2O (700 mL) and stirred at 25° C. for 30 min, the solids were removed by filtration and the filtrate was dried over MgSO4 and filtered again. The final filtrate was concentrated to yield (1R)-1-(4-piperidinyl)ethanol (22 g, 57% yield) as a light beige solid. 1H NMR (400 MHz, CDCl3): δ 3.50 (quint, 1H, J=6.3 Hz), 3.13-3.01 (m, 2H), 2.61-2.47 (m, 2H), 1.88 (br, 2H), 1.84-1.73 (m, 1H), 1.63-1.52 (m, 1H), 1.41-1.27 (m, 1H), 1.23-1.05 (m, 2H), 1.13 (d, 3H, J=6.2 Hz). The mixture was evacuated purged with hydrogen several times The mixture was filtered to remove catalyst the filtrate was concentrated in vacuo triturated with EtOAc to yield a cream-colored solid which was collected by filtration The filter cake was dissolved in MeOH (500 mL) 50% NaOH (15.8 g) was added The resulting solution was stirred at 25° C. for 30 min concentrated The resulting solid was triturated with Et2O (700 mL) stirred at 25° C. for 30 min the solids were removed by filtration the filtrate was dried over MgSO4 filtered again The final filtrate was concentrated

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

Procedure: A solution of 3-(1-methylethyl)-5-(trichloromethyl)-1,2,4-oxadiazole (25.8 g, 112 mmol) and (1R)-1-(4-piperidinyl)ethanol (13.4 g, 104 mmol) in MeOH (15 mL) was stirred at ambient temperature under a stream of nitrogen for 7 days. The reaction was diluted with MeOH (40 mL), cooled in an ice bath and 1N NaOH (25 mL) was added. The mixture was allowed to warm to ambient temperature and stir for 1 h. The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) and the layers were separated. The aqueous layer was saturated with NaCl and extracted with EtOAc (200 mL). The combined EtOAc layers were dried over MgSO4, concentrated and placed under high vacuum for 18 h to afford (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethanol (16.75 g, 68%) as an orange oil. 1H NMR (400 MHz, CDCl3): δ 4.14 (m, 2H), 3.57 (quint, 1H, J=6.3 Hz), 2.98 (m, 2H), 2.83 (septet, 1H, J=7.0 Hz), 1.90 (m, 1H), 1.86 (br, 1H), 1.67 (m, 1H), 1.45 (m, 1H), 1.33 (m, 2H), 1.23 (d, 6H, J=7.0 Hz), 1.16 (d, 3H, J=6.3 Hz); LRMS (ESI), m/z 240 (M+H). cooled in an ice bath The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) the layers were separated extracted with EtOAc (200 mL) The combined EtOAc layers were dried over MgSO4 concentrated placed under high vacuum for 18 h

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

Procedure: A solution of (1R)-1-(4-pyridinyl)ethanol (37 g, 0.3 mol, 78% ee) in MeOH (2 L) was charged with PtO2 (5 g) under nitrogen atmosphere followed by acetic acid (19 mL). The mixture was evacuated and purged with hydrogen several times and then stirred under an atmosphere of hydrogen for 2 d at room temperature. The mixture was filtered to remove catalyst and the filtrate was concentrated in vacuo and triturated with EtOAc to yield a cream-colored solid which was collected by filtration. The filter cake was dissolved in MeOH (500 mL) and 50% NaOH (15.8 g) was added. The resulting solution was stirred at 25° C. for 30 min and concentrated. The resulting solid was triturated with Et2O (700 mL) and stirred at 25° C. for 30 min, the solids were removed by filtration and the filtrate was dried over MgSO4 and filtered again. The final filtrate was concentrated to yield (1R)-1-(4-piperidinyl)ethanol (22 g, 57% yield) as a light beige solid. 1H NMR (400 MHz, CDCl3): δ 3.50 (quint, 1H, J=6.3 Hz), 3.13-3.01 (m, 2H), 2.61-2.47 (m, 2H), 1.88 (br, 2H), 1.84-1.73 (m, 1H), 1.63-1.52 (m, 1H), 1.41-1.27 (m, 1H), 1.23-1.05 (m, 2H), 1.13 (d, 3H, J=6.2 Hz). The mixture was evacuated purged with hydrogen several times The mixture was filtered to remove catalyst the filtrate was concentrated in vacuo triturated with EtOAc to yield a cream-colored solid which was collected by filtration The filter cake was dissolved in MeOH (500 mL) 50% NaOH (15.8 g) was added The resulting solution was stirred at 25° C. for 30 min concentrated The resulting solid was triturated with Et2O (700 mL) stirred at 25° C. for 30 min the solids were removed by filtration the filtrate was dried over MgSO4 filtered again The final filtrate was concentrated