3,3-dichloropiperidin-2-one

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To valerolactam (5.6 g, 55 mmol) in CHCl3 was added PCl5 (34.6 g, 166 mmol) and the reaction was heated to reflux 24 h. The reaction was cooled, quenched with H2O, extracted with CHCl3 and dried (MgSO4) to afford crude 3,3-dichloro-2-piperidinone. the reaction was heated to reflux 24 h The reaction was cooled quenched with H2O extracted with CHCl3 dried (MgSO4)

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

実験手順: Part A. δ-Valerolactam (22.22 g, 222.89 mmol) was stirred in CHCl3 (500 mL) at 0° C. PCl5 (140.0 g, 68.29 mmol) was added portionwise. The resulting slurry was stirred at reflux for 3 h until the solution became clear. The mixture was cooled in an ice bath and H2O was added carefully until the PCl5 was quenched completely. The two layers were separated. The organic layer was washed with H2O (3×) and brine (2×), dried over MgSO4, filtered, and concentrated to dryness to give 3,3-dichloro-2-piperidinone (31.63 g, yield: 85%). This solid (16.50 g, 98.80 mmol) was dissolved in DMF (20 mL), and Li2CO3 (21.93 g, 296.40 mmol, 3.0 eq) was added. The mixture was stirred at 120° C. for 1 day. The solvent was further concentrated, and 1N HCl was added to acidify the mixture. It was then extracted with CHCl3 (6×). The organic layers were washed with H2O, brine, dried over MgSO4, and concentrated to dryness to give almost pure 3-chloro-5,6-dihydro-2(1H)-pyridinone (11.13 g, 87%). at reflux for 3 h until the solution The mixture was cooled in an ice bath was quenched completely The two layers were separated The organic layer was washed with H2O (3×) and brine (2×) dried over MgSO4 filtered concentrated to dryness

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

実験手順: Part A. δ-Valerolactam (22.22 g, 222.89 mmol) was stirred in CHCl3 (500 mL) at 0° C. PCl5 (140.0 g, 68.29 mmol) was added portionwise. The resulting slurry was stirred at reflux for 3 h until the solution became clear. The mixture was cooled in an ice bath and H2O was added carefully until the PCl5 was quenched completely. The two layers were separated. The organic layer was washed with H2O (3×) and brine (2×), dried over MgSO4, filtered, and concentrated to dryness to give 3,3-dichloro-2-piperidinone (31.63 g, yield: 85%). This solid (16.50 g, 98.80 mmol) was dissolved in DMF (20 mL), and Li2CO3 (21.93 g, 296.40 mmol, 3.0 eq) was added. The mixture was stirred at 120° C. for 1 day. The solvent was further concentrated, and 1N HCl was added to acidify the mixture. It was then extracted with CHCl3 (6×). The organic layers were washed with H2O, brine, dried over MgSO4, and concentrated to dryness to give almost pure 3-chloro-5,6-dihydro-2(1H)-pyridinone (11.13 g, 87%). at reflux for 3 h until the solution The mixture was cooled in an ice bath was quenched completely The two layers were separated The organic layer was washed with H2O (3×) and brine (2×) dried over MgSO4 filtered concentrated to dryness

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of piperidin-2-one (42, 25.0 g, 252.2 mmol) in CHCl3 (250 mL) was treated with PCl5 (158 g, 756.5 mmol, 3.0 equiv) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for 10 min before being warmed up to reflux for 2 h. When HPLC showed the reaction was complete, the reaction mixture was cooled down to 5-10° C. before being transferred into an ice water (500 mL) with caution. The resulting mixture was stirred at 0-5° C. for 1 h before being gradually warmed up to room temperature for 12 h. The two layers were separated, and the aqueous layer was extracted with CH2Cl2 (4×50 mL). The combined organic extracts were washed with saturated NaCl aqueous solution (50 mL), dried over MgSO4, and concentrated in vacuo. The residual solids were treated with 30% EtOAc/hexane (50 mL) before being collected by filtration. The crude pale-yellow solids were dried in vacuo at 30-35° C. for 12 h to afford the desired 3,3-dichloro-piperidin-2-one (43, 27.96 g, 42.36 g theoretical, 66%) as bright-yellow oil, which solidified upon standing at room temperature in vacuo. For 43, CIMS m/z 166/170 (M+−H, C5H7Cl2NO). the resulting reaction mixture before being warmed up to reflux for 2 h the reaction mixture was cooled down to 5-10° C. The resulting mixture was stirred at 0-5° C. for 1 h before being gradually warmed up to room temperature for 12 h The two layers were separated the aqueous layer was extracted with CH2Cl2 (4×50 mL) The combined organic extracts were washed with saturated NaCl aqueous solution (50 mL) dried over MgSO4 concentrated in vacuo The residual solids were treated with 30% EtOAc/hexane (50 mL) before being collected by filtration The crude pale-yellow solids were dried in vacuo at 30-35° C. for 12 h

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

実験手順: Part A. To valerolactam (5.6 g, 55 mmol) in CHCl3 was added PCl5 (34.6 g, 166 mmol) and the reaction was heated to reflux 24 h. The reaction was cooled, quenched with H2O, extracted with CHCl3 and dried (MgSO4) to afford crude 3,3-dichloro-2-piperidinone. the reaction was heated to reflux 24 h The reaction was cooled quenched with H2O extracted with CHCl3 dried (MgSO4)

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

実験手順: A solution of piperidin-2-one (42, 25.0 g, 252.2 mmol) in CHCl3 (250 mL) was treated with PCl5 (158 g, 756.5 mmol, 3.0 equiv) at 0–5° C., and the resulting reaction mixture was stirred at 0–5° C. for 10 min before being warmed up to reflux for 2 h. When HPLC showed the reaction was complete, the reaction mixture was cooled down to 5–10° C. before being transferred into an ice water (500 mL) with caution. The resulting mixture was stirred at 0–5° C. for 1 h before being gradually warmed up to room temperature for 12 h. The two layers were separated, and the aqueous layer was extracted with CH2Cl2(4×50 mL). The combined organic extracts were washed with saturated NaCl aqueous solution (50 mL), dried over MgSO4, and concentrated in vacuo. The residual solids were treated with 30% EtOAc/hexane (50 mL) before being collected by filtration. The crude pale-yellow solids were dried in vacuo at 30–35° C. for 12 h to afford the desired 3,3-dichloro-piperidin-2-one (43, 27.96 g, 42.36 g theoretical, 66%) as bright-yellow oil, which solidified upon standing at room temperature in vacuo. For 43, CIMS m/z 166/170 (M+−H, C5H7Cl2NO). the resulting reaction mixture before being warmed up to reflux for 2 h the reaction mixture was cooled down to 5–10° C. The resulting mixture was stirred at 0–5° C. for 1 h The two layers were separated the aqueous layer was extracted with CH2Cl2(4×50 mL) The combined organic extracts were washed with saturated NaCl aqueous solution (50 mL) dried over MgSO4 concentrated in vacuo The residual solids were treated with 30% EtOAc/hexane (50 mL) before being collected by filtration The crude pale-yellow solids were dried in vacuo at 30–35° C. for 12 h

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

実験手順: Part A. To valerolactam (5.6 g, 55 mmol) in CHCl3 was added PCl5 (34.6 g, 166 mmol) and the reaction was heated to reflux 24 h. The reaction was cooled, quenched with H2O, extracted with CHCl3 and dried (MgSO4) to afford crude 3,3-dichloro-2-piperidinone. the reaction was heated to reflux 24 h The reaction was cooled quenched with H2O extracted with CHCl3 dried (MgSO4)

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

実験手順: Part A. To valerolactam (5.6 g, 55 mmol) in CHCl3 was added PCl5 (34.6 g, 166 mmol) and the reaction was heated to reflux 24 h. The reaction was cooled, quenched with H2O, extracted with CHCl3 and dried (MgSO4) to afford crude 3,3-dichloro-2-piperidinone. the reaction was heated to reflux 24 h The reaction was cooled quenched with H2O extracted with CHCl3 dried (MgSO4)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Part A. To valerolactam (5.6 g, 55 mmol) in CHCl3 was added PCl5 (34.6 g, 166 mmol) and the reaction was heated to reflux 24 h. The reaction was cooled, quenched with H2O, extracted with CHCl3 and dried (MgSO4) to afford crude 3,3-dichloro-2-piperidinone. the reaction was heated to reflux 24 h The reaction was cooled quenched with H2O extracted with CHCl3 dried (MgSO4)

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

実験手順: Part A. To valerolactam (5.6 g, 55 mmol) in CHCl3 was added PCl5 (34.6 g, 166 mmol) and the reaction was heated to reflux 24 h. The reaction was cooled, quenched with H2O, extracted with CHCl3 and dried (MgSO4) to afford crude 3,3-dichloro-2-piperidinone. the reaction was heated to reflux 24 h The reaction was cooled quenched with H2O extracted with CHCl3 dried (MgSO4)