2-(1-methylpiperidin-4-yl)ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: NaH (60% dispersion in mineral-oil, 0.81 g, 42.2 mmol) was suspended in heptane (10 mL) under an argon atmosphere. The heptane was decanted off, and the flask was charged with THF (20 mL) and cooled to 0° C. A solution of 2-(1-methyl-piperidin-4-yl)-ethanol (1.01 g, 7.03 mmol) in THF (20 mL) was added drop-wise, followed by a solution of 4-nitrophenyl 4-(4-methylphenyl)piperazine-1-carboxylate (2.89 g, 8.46 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature and stirred for 48 hours. The reaction mixture was then cooled to 0° C. and quenched with the drop-wise addition of sat aq NaHCO3 solution and concentrated in vacuo. The residue was dissolved in EtOAc (200 mL), washed with a NaHCO3 solution (4×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 90:10 mixture of DCM:MeOH) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give the title compound 2-(1-methylpiperidin-4-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (0.21 g, 7%) as a cream solid. The heptane was decanted off the flask was charged with THF (20 mL) to warm to room temperature The reaction mixture was then cooled to 0° C. quenched with the drop-wise addition of sat aq NaHCO3 solution concentrated in vacuo The residue was dissolved in EtOAc (200 mL) washed with a NaHCO3 solution (4×50 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 90:10 mixture of DCM eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%) The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Piperidin-4-yl-ethanol (2.37 g, 18.3 mmol) was dissolved in formic acid (2.1 mL, 55.7 mmol), 35% aqueous formaldehyde solution (4.5 mL, 55.4 mmol) and water (20 mL). The reaction mixture was heated at 95° C. for 2 hours, and then cooled to room temperature. The reaction mixture was quenched by slowly pouring it onto a saturated NaHCO3 solution (200 mL) and concentrated in vacuo. The residue was suspended in MeOH (100 mL) and stirred for 2 hours, filtered, and the filtrate was concentrated in vacuo to give 2-(1-methyl-piperidin-4-yl)-ethanol (3.38 g, 129%) as a colourless oil which was used without further purification. cooled to room temperature The reaction mixture was quenched by slowly pouring it onto a saturated NaHCO3 solution (200 mL) concentrated in vacuo filtered the filtrate was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: LAH (2.25 g, 59.3 mmol) was slowly added to 150 mL of THF. (1-Methyl-piperidin-4-yl)-acetic acid methyl ester (Step B) in 30 mL of THF was added dropwise to the LAH in THF and the resulting mixture was stirred for 4 h. Water (2.26 mL), 2.26 mL of 15% NaOH and 6.78 mL of water were carefully added and stirring was continued for 30 min. The mixture was filtered through Celite®, the solids were washed with EtOAc and the filtrate was evaporated, giving 2-(1-methyl-piperidin-4-yl)-ethanol as a yellow oil. stirring was continued for 30 min The mixture was filtered through Celite® the solids were washed with EtOAc the filtrate was evaporated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: NaH (60% dispersion in mineral-oil, 0.81 g, 42.2 mmol) was suspended in heptane (10 mL) under an argon atmosphere. The heptane was decanted off, and the flask was charged with THF (20 mL) and cooled to 0° C. A solution of 2-(1-methyl-piperidin-4-yl)-ethanol (1.01 g, 7.03 mmol) in THF (20 mL) was added drop-wise, followed by a solution of 4-nitrophenyl 4-(4-methylphenyl)piperazine-1-carboxylate (2.89 g, 8.46 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature and stirred for 48 hours. The reaction mixture was then cooled to 0° C. and quenched with the drop-wise addition of sat aq NaHCO3 solution and concentrated in vacuo. The residue was dissolved in EtOAc (200 mL), washed with a NaHCO3 solution (4×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 90:10 mixture of DCM:MeOH) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give the title compound 2-(1-methylpiperidin-4-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (0.21 g, 7%) as a cream solid. The heptane was decanted off the flask was charged with THF (20 mL) to warm to room temperature The reaction mixture was then cooled to 0° C. quenched with the drop-wise addition of sat aq NaHCO3 solution concentrated in vacuo The residue was dissolved in EtOAc (200 mL) washed with a NaHCO3 solution (4×50 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 90:10 mixture of DCM eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%) The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: NaH (60% dispersion in mineral-oil, 0.81 g, 42.2 mmol) was suspended in heptane (10 mL) under an argon atmosphere. The heptane was decanted off, and the flask was charged with THF (20 mL) and cooled to 0° C. A solution of 2-(1-methyl-piperidin-4-yl)-ethanol (1.01 g, 7.03 mmol) in THF (20 mL) was added drop-wise, followed by a solution of 4-nitrophenyl 4-(4-methylphenyl)piperazine-1-carboxylate (2.89 g, 8.46 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature and stirred for 48 hours. The reaction mixture was then cooled to 0° C. and quenched with the drop-wise addition of sat aq NaHCO3 solution and concentrated in vacuo. The residue was dissolved in EtOAc (200 mL), washed with a NaHCO3 solution (4×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 90:10 mixture of DCM:MeOH) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give the title compound 2-(1-methylpiperidin-4-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (0.21 g, 7%) as a cream solid. The heptane was decanted off the flask was charged with THF (20 mL) to warm to room temperature The reaction mixture was then cooled to 0° C. quenched with the drop-wise addition of sat aq NaHCO3 solution concentrated in vacuo The residue was dissolved in EtOAc (200 mL) washed with a NaHCO3 solution (4×50 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 90:10 mixture of DCM eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%) The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Piperidin-4-yl-ethanol (2.37 g, 18.3 mmol) was dissolved in formic acid (2.1 mL, 55.7 mmol), 35% aqueous formaldehyde solution (4.5 mL, 55.4 mmol) and water (20 mL). The reaction mixture was heated at 95° C. for 2 hours, and then cooled to room temperature. The reaction mixture was quenched by slowly pouring it onto a saturated NaHCO3 solution (200 mL) and concentrated in vacuo. The residue was suspended in MeOH (100 mL) and stirred for 2 hours, filtered, and the filtrate was concentrated in vacuo to give 2-(1-methyl-piperidin-4-yl)-ethanol (3.38 g, 129%) as a colourless oil which was used without further purification. cooled to room temperature The reaction mixture was quenched by slowly pouring it onto a saturated NaHCO3 solution (200 mL) concentrated in vacuo filtered the filtrate was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: LAH (2.25 g, 59.3 mmol) was slowly added to 150 mL of THF. (1-Methyl-piperidin-4-yl)-acetic acid methyl ester (Step B) in 30 mL of THF was added dropwise to the LAH in THF and the resulting mixture was stirred for 4 h. Water (2.26 mL), 2.26 mL of 15% NaOH and 6.78 mL of water were carefully added and stirring was continued for 30 min. The mixture was filtered through Celite®, the solids were washed with EtOAc and the filtrate was evaporated, giving 2-(1-methyl-piperidin-4-yl)-ethanol as a yellow oil. stirring was continued for 30 min The mixture was filtered through Celite® the solids were washed with EtOAc the filtrate was evaporated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: NaH (60% dispersion in mineral-oil, 0.81 g, 42.2 mmol) was suspended in heptane (10 mL) under an argon atmosphere. The heptane was decanted off, and the flask was charged with THF (20 mL) and cooled to 0° C. A solution of 2-(1-methyl-piperidin-4-yl)-ethanol (1.01 g, 7.03 mmol) in THF (20 mL) was added drop-wise, followed by a solution of 4-nitrophenyl 4-(4-methylphenyl)piperazine-1-carboxylate (2.89 g, 8.46 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature and stirred for 48 hours. The reaction mixture was then cooled to 0° C. and quenched with the drop-wise addition of sat aq NaHCO3 solution and concentrated in vacuo. The residue was dissolved in EtOAc (200 mL), washed with a NaHCO3 solution (4×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 90:10 mixture of DCM:MeOH) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give the title compound 2-(1-methylpiperidin-4-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (0.21 g, 7%) as a cream solid. The heptane was decanted off the flask was charged with THF (20 mL) to warm to room temperature The reaction mixture was then cooled to 0° C. quenched with the drop-wise addition of sat aq NaHCO3 solution concentrated in vacuo The residue was dissolved in EtOAc (200 mL) washed with a NaHCO3 solution (4×50 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 90:10 mixture of DCM eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%) The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Piperidin-4-yl-ethanol (2.37 g, 18.3 mmol) was dissolved in formic acid (2.1 mL, 55.7 mmol), 35% aqueous formaldehyde solution (4.5 mL, 55.4 mmol) and water (20 mL). The reaction mixture was heated at 95° C. for 2 hours, and then cooled to room temperature. The reaction mixture was quenched by slowly pouring it onto a saturated NaHCO3 solution (200 mL) and concentrated in vacuo. The residue was suspended in MeOH (100 mL) and stirred for 2 hours, filtered, and the filtrate was concentrated in vacuo to give 2-(1-methyl-piperidin-4-yl)-ethanol (3.38 g, 129%) as a colourless oil which was used without further purification. cooled to room temperature The reaction mixture was quenched by slowly pouring it onto a saturated NaHCO3 solution (200 mL) concentrated in vacuo filtered the filtrate was concentrated in vacuo