[1-(2-methoxyethyl)piperidin-4-yl]methanol

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

Procedure: To a solution of (1-(2-methoxyethyl)piperidin-4-yl)methanol (3.65 g, 21.1 mmol) and NMM (2.5 mL, 22.8 mmol) in DCM (100 mL) at 0° C. was added p-nitrophenyl chloroformate. The reaction mixture was stirred at room temperature overnight and then washed sequentially with sat aq NaHCO3 solution (5×100 mL), dried (MgSO4) and concentrated in vacuo. The resulting orange oil was recrystallised from EtOAc and heptane to give (1-(2-methoxyethyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (3.65 g, 51%) as an orange solid. washed sequentially with sat aq NaHCO3 solution (5×100 mL) dried (MgSO4) concentrated in vacuo The resulting orange oil was recrystallised from EtOAc and heptane

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

Procedure: A solution of (1-(2-methoxyacetyl)piperidin-4-yl)methyl 2-methoxyacetate from the previous step (6.5 g, 25.1 mmol) in THF (10 mL) was added drop-wise to a 1 M solution of LiAlH4 in THF (55.0 mL, 55.0 mmol) under argon. The reaction mixture was stirred at room temperature for 2 days and then cooled to 0° C. Water (2.0 mL) was added drop-wise. A gelatinous white solid formed. 0.2M aq NaOH solution (2.0 mL) was added drop-wise. Water (5.0 mL) was added and the resulting mixture stirred at room temperature for 3 h. The white solid was removed by filtration. The filtrate was concentrated in vacuo and dried on an Isolute HM-N cartridge (eluting with EtOAc). The resulting organic solution was dried in vacuo to give (1-(2-methoxyethyl)piperidin-4-yl)methanol (3.65 mg, 84%) as a yellow oil. cooled to 0° C A gelatinous white solid formed the resulting mixture stirred at room temperature for 3 h The white solid was removed by filtration The filtrate was concentrated in vacuo dried on an Isolute HM-N cartridge (eluting with EtOAc) The resulting organic solution was dried in vacuo

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

Procedure: To a solution of (1-(2-methoxyethyl)piperidin-4-yl)methanol (3.65 g, 21.1 mmol) and NMM (2.5 mL, 22.8 mmol) in DCM (100 mL) at 0° C. was added p-nitrophenyl chloroformate. The reaction mixture was stirred at room temperature overnight and then washed sequentially with sat aq NaHCO3 solution (5×100 mL), dried (MgSO4) and concentrated in vacuo. The resulting orange oil was recrystallised from EtOAc and heptane to give (1-(2-methoxyethyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (3.65 g, 51%) as an orange solid. washed sequentially with sat aq NaHCO3 solution (5×100 mL) dried (MgSO4) concentrated in vacuo The resulting orange oil was recrystallised from EtOAc and heptane

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

Procedure: To a solution of (1-(2-methoxyethyl)piperidin-4-yl)methanol (3.65 g, 21.1 mmol) and NMM (2.5 mL, 22.8 mmol) in DCM (100 mL) at 0° C. was added p-nitrophenyl chloroformate. The reaction mixture was stirred at room temperature overnight and then washed sequentially with sat aq NaHCO3 solution (5×100 mL), dried (MgSO4) and concentrated in vacuo. The resulting orange oil was recrystallised from EtOAc and heptane to give (1-(2-methoxyethyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (3.65 g, 51%) as an orange solid. washed sequentially with sat aq NaHCO3 solution (5×100 mL) dried (MgSO4) concentrated in vacuo The resulting orange oil was recrystallised from EtOAc and heptane

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

Procedure: A solution of (1-(2-methoxyacetyl)piperidin-4-yl)methyl 2-methoxyacetate from the previous step (6.5 g, 25.1 mmol) in THF (10 mL) was added drop-wise to a 1 M solution of LiAlH4 in THF (55.0 mL, 55.0 mmol) under argon. The reaction mixture was stirred at room temperature for 2 days and then cooled to 0° C. Water (2.0 mL) was added drop-wise. A gelatinous white solid formed. 0.2M aq NaOH solution (2.0 mL) was added drop-wise. Water (5.0 mL) was added and the resulting mixture stirred at room temperature for 3 h. The white solid was removed by filtration. The filtrate was concentrated in vacuo and dried on an Isolute HM-N cartridge (eluting with EtOAc). The resulting organic solution was dried in vacuo to give (1-(2-methoxyethyl)piperidin-4-yl)methanol (3.65 mg, 84%) as a yellow oil. cooled to 0° C A gelatinous white solid formed the resulting mixture stirred at room temperature for 3 h The white solid was removed by filtration The filtrate was concentrated in vacuo dried on an Isolute HM-N cartridge (eluting with EtOAc) The resulting organic solution was dried in vacuo

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

Procedure: To a solution of (1-(2-methoxyethyl)piperidin-4-yl)methanol (3.65 g, 21.1 mmol) and NMM (2.5 mL, 22.8 mmol) in DCM (100 mL) at 0° C. was added p-nitrophenyl chloroformate. The reaction mixture was stirred at room temperature overnight and then washed sequentially with sat aq NaHCO3 solution (5×100 mL), dried (MgSO4) and concentrated in vacuo. The resulting orange oil was recrystallised from EtOAc and heptane to give (1-(2-methoxyethyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (3.65 g, 51%) as an orange solid. washed sequentially with sat aq NaHCO3 solution (5×100 mL) dried (MgSO4) concentrated in vacuo The resulting orange oil was recrystallised from EtOAc and heptane

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

Procedure: A solution of (1-(2-methoxyacetyl)piperidin-4-yl)methyl 2-methoxyacetate from the previous step (6.5 g, 25.1 mmol) in THF (10 mL) was added drop-wise to a 1 M solution of LiAlH4 in THF (55.0 mL, 55.0 mmol) under argon. The reaction mixture was stirred at room temperature for 2 days and then cooled to 0° C. Water (2.0 mL) was added drop-wise. A gelatinous white solid formed. 0.2M aq NaOH solution (2.0 mL) was added drop-wise. Water (5.0 mL) was added and the resulting mixture stirred at room temperature for 3 h. The white solid was removed by filtration. The filtrate was concentrated in vacuo and dried on an Isolute HM-N cartridge (eluting with EtOAc). The resulting organic solution was dried in vacuo to give (1-(2-methoxyethyl)piperidin-4-yl)methanol (3.65 mg, 84%) as a yellow oil. cooled to 0° C A gelatinous white solid formed the resulting mixture stirred at room temperature for 3 h The white solid was removed by filtration The filtrate was concentrated in vacuo dried on an Isolute HM-N cartridge (eluting with EtOAc) The resulting organic solution was dried in vacuo