ethyl 2-phenyl-2-piperidin-1-ylacetate

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

実験手順: Ethyl 2-phenyl-2-(piperidin-1-yl)acetate (985 mg, 3.98 mmol) was dissolved in dioxane (33 ml) and 37% HCl (10 ml) was slowly added. The reaction was refluxed for 48 hours and then it was evaporated under reduced pressure. The residue was triturated with acetonitrile (15 ml) and the solid was collected by filtration to obtain 2-phenyl-2-(piperidin-1-yl)acetic acid hydrochloride (876 mg, 86% yield) as a off-white solid. 1H NMR (300 MHz, DMSO-d6) ppm 10.57 (br. s., 1H), 7.33-7.67 (m, 5H), 5.27 (s, 1H), 2.84-3.21 (m, 4H), 1.64-1.98 (m, 4H), 1.31-1.64 (m, 2H) The reaction was refluxed for 48 hours it was evaporated under reduced pressure The residue was triturated with acetonitrile (15 ml) the solid was collected by filtration

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

実験手順: DIPEA (0.86 ml, 4.94 mmol) and piperidine (0.49 ml, 4.94 mmol) were sequentially added to a solution of ethyl 2-bromo-2-phenylacetate (0.72 ml, 4.11 mmol) in acetonitrile (13 ml). The pale yellow solution was stirred at room temperature monitoring by TLC (petroleum ether/EtOAc=9/1). After 1.5 hours complete conversion into the desired product was detected. Solvent was evaporated and the residue (pale yellow solid) was triturated with Et20 (30 ml). The solid was filtered off and the ethereal solution was evaporated to dryness. The residue was purified by flash chromatography (petroleum ether/EtOAc=95/5) to collect ethyl 2-phenyl-2-(piperidin-1-yl)acetate (990 mg, 97% yield) as a colorless oil.

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

実験手順: To a solution of ethyl 2-bromo-2-phenylacetate 21 (1.50 g, 6.17 mmol) in THF (10 mL) at room temperature was added piperidine (0.641 mL, 6.48 mmol) and TEA (1.72 mL, 12.34 mmol) and the reaction mixture was stirred for 3 h then diluted with brine and extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude material was purified by silica gel column chromatography with gradient of ethyl acetate (0-50%) in hexane to afford 22 as a colorless viscous oil (520 mg, 34%). LRMS (ESI): (calc) 247.3 (found) 248.3 (MH)+. extracted with ethyl acetate The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica gel column chromatography with gradient of ethyl acetate (0-50%) in hexane

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

実験手順: Ethyl 2-phenyl-2-(piperidin-1-yl)acetate (985 mg, 3.98 mmol) was dissolved in dioxane (33 ml) and 37% HCl (10 ml) was slowly added. The reaction was refluxed for 48 hours and then it was evaporated under reduced pressure. The residue was triturated with acetonitrile (15 ml) and the solid was collected by filtration to obtain 2-phenyl-2-(piperidin-1-yl)acetic acid hydrochloride (876 mg, 86% yield) as a off-white solid. 1H NMR (300 MHz, DMSO-d6) ppm 10.57 (br. s., 1H), 7.33-7.67 (m, 5H), 5.27 (s, 1H), 2.84-3.21 (m, 4H), 1.64-1.98 (m, 4H), 1.31-1.64 (m, 2H) The reaction was refluxed for 48 hours it was evaporated under reduced pressure The residue was triturated with acetonitrile (15 ml) the solid was collected by filtration

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

実験手順: DIPEA (0.86 ml, 4.94 mmol) and piperidine (0.49 ml, 4.94 mmol) were sequentially added to a solution of ethyl 2-bromo-2-phenylacetate (0.72 ml, 4.11 mmol) in acetonitrile (13 ml). The pale yellow solution was stirred at room temperature monitoring by TLC (petroleum ether/EtOAc=9/1). After 1.5 hours complete conversion into the desired product was detected. Solvent was evaporated and the residue (pale yellow solid) was triturated with Et20 (30 ml). The solid was filtered off and the ethereal solution was evaporated to dryness. The residue was purified by flash chromatography (petroleum ether/EtOAc=95/5) to collect ethyl 2-phenyl-2-(piperidin-1-yl)acetate (990 mg, 97% yield) as a colorless oil.

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

実験手順: DIPEA (0.86 ml, 4.94 mmol) and piperidine (0.49 ml, 4.94 mmol) were sequentially added to a solution of ethyl 2-bromo-2-phenylacetate (0.72 ml, 4.11 mmol) in acetonitrile (13 ml). The pale yellow solution was stirred at room temperature monitoring by TLC (petroleum ether/EtOAc=9/1). After 1.5 hours complete conversion into the desired product was detected. Solvent was evaporated and the residue (pale yellow solid) was triturated with Et20 (30 ml). The solid was filtered off and the ethereal solution was evaporated to dryness. The residue was purified by flash chromatography (petroleum ether/EtOAc=95/5) to collect ethyl 2-phenyl-2-(piperidin-1-yl)acetate (990 mg, 97% yield) as a colorless oil.

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

実験手順: To a solution of ethyl 2-bromo-2-phenylacetate 21 (1.50 g, 6.17 mmol) in THF (10 mL) at room temperature was added piperidine (0.641 mL, 6.48 mmol) and TEA (1.72 mL, 12.34 mmol) and the reaction mixture was stirred for 3 h then diluted with brine and extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude material was purified by silica gel column chromatography with gradient of ethyl acetate (0-50%) in hexane to afford 22 as a colorless viscous oil (520 mg, 34%). LRMS (ESI): (calc) 247.3 (found) 248.3 (MH)+. extracted with ethyl acetate The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica gel column chromatography with gradient of ethyl acetate (0-50%) in hexane

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

実験手順: Ethyl 2-phenyl-2-(piperidin-1-yl)acetate (985 mg, 3.98 mmol) was dissolved in dioxane (33 ml) and 37% HCl (10 ml) was slowly added. The reaction was refluxed for 48 hours and then it was evaporated under reduced pressure. The residue was triturated with acetonitrile (15 ml) and the solid was collected by filtration to obtain 2-phenyl-2-(piperidin-1-yl)acetic acid hydrochloride (876 mg, 86% yield) as a off-white solid. 1H NMR (300 MHz, DMSO-d6) ppm 10.57 (br. s., 1H), 7.33-7.67 (m, 5H), 5.27 (s, 1H), 2.84-3.21 (m, 4H), 1.64-1.98 (m, 4H), 1.31-1.64 (m, 2H) The reaction was refluxed for 48 hours it was evaporated under reduced pressure The residue was triturated with acetonitrile (15 ml) the solid was collected by filtration

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

実験手順: DIPEA (0.86 ml, 4.94 mmol) and piperidine (0.49 ml, 4.94 mmol) were sequentially added to a solution of ethyl 2-bromo-2-phenylacetate (0.72 ml, 4.11 mmol) in acetonitrile (13 ml). The pale yellow solution was stirred at room temperature monitoring by TLC (petroleum ether/EtOAc=9/1). After 1.5 hours complete conversion into the desired product was detected. Solvent was evaporated and the residue (pale yellow solid) was triturated with Et20 (30 ml). The solid was filtered off and the ethereal solution was evaporated to dryness. The residue was purified by flash chromatography (petroleum ether/EtOAc=95/5) to collect ethyl 2-phenyl-2-(piperidin-1-yl)acetate (990 mg, 97% yield) as a colorless oil.