3-benzylpiperidin-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: A solution of 1,3-diphenylmethyl-2-piperidinone (2.79 g, 10 mmol) in dry THF (25 mL) was added at -78° C. to a well stirred solution of Li metal (0.70 g, 100 mmol) in liquid NH3 (200 mL). After 15 min, the cooling bath was removed, and the NH3 was allowed to escape (ca. 2 h). The resulting colorless residue was treated with saturated NH4Cl (50 mL), and extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine (25 mL), dried over MgSO4, and concentrated in vacuo to give 2.78 g of brown viscous residue. Flash chromatography over silica gel (1% MeOH in CHCl3 -EtOAc, 1:1) afforded the lactam (See: Rodrequez M, Heitz A, Martinez J (1992) supra)(0.87 g, 46% ) as a colorless solid: mp 120-122° C. (CH2Cl2 -hexanes). the cooling bath was removed (ca. 2 h) The resulting colorless residue was treated with saturated NH4Cl (50 mL) extracted with EtOAc (3×50 mL) The combined organic extract was washed with brine (25 mL) dried over MgSO4 concentrated in vacuo

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

実験手順: A solution of 1,3-diphenylmethyl-2-piperidinone (2.79 g, 10 mmol) in dry THF (25 mL) was added at -78° C. to a well stirred solution of Li metal (0.70 g, 100 mmol) in liquid NH3 (200 mL). After 15 min, the cooling bath was removed, and the NH3 was allowed to escape (ca. 2 h). The resulting colorless residue was treated with saturated NH4Cl (50 mL), and extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine (25 mL), dried over MgSO4, and concentrated in vacuo to give 2.78 g of brown viscous residue. Flash chromatography over silica gel (1% MeOH in CHCl3 -EtOAc, 1:1) afforded the lactam (See: Rodrequez M, Heitz A, Martinez J (1992) supra)(0.87 g, 46% ) as a colorless solid: mp 120-122° C. (CH2Cl2 -hexanes). the cooling bath was removed (ca. 2 h) The resulting colorless residue was treated with saturated NH4Cl (50 mL) extracted with EtOAc (3×50 mL) The combined organic extract was washed with brine (25 mL) dried over MgSO4 concentrated in vacuo

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: A solution of 1,3-diphenylmethyl-2-piperidinone (2.79 g, 10 mmol) in dry THF (25 mL) was added at -78° C. to a well stirred solution of Li metal (0.70 g, 100 mmol) in liquid NH3 (200 mL). After 15 min, the cooling bath was removed, and the NH3 was allowed to escape (ca. 2 h). The resulting colorless residue was treated with saturated NH4Cl (50 mL), and extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine (25 mL), dried over MgSO4, and concentrated in vacuo to give 2.78 g of brown viscous residue. Flash chromatography over silica gel (1% MeOH in CHCl3 -EtOAc, 1:1) afforded the lactam (See: Rodriquez m, Heitz A, Martinez J (1992) supra) (0.87 g, 46% ) as a colorless solid: mp 120°-122° C. (CH2Cl2 -hexanes). the cooling bath was removed (ca. 2 h) The resulting colorless residue was treated with saturated NH4Cl (50 mL) extracted with EtOAc (3×50 mL) The combined organic extract was washed with brine (25 mL) dried over MgSO4 concentrated in vacuo

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

実験手順: This example describes the preparation of I where n=2 and R1=phenyl. In a nitrogen-filled glove box, a Fisher-Porter tube was charged with iridium catalyst prepared as in Example 1 (10 mg, 0.012 mmol) and 3-(benzylidene)-2-piperidone (250 mg, 1.3 mmol). Methanol (3 mL) and dichloromethane (3 mL) were added and the system was flushed 4 times with hydrogen and pressured to 60 psi (0.5 MPa) H2. After 18 h the reaction mixture was filtered through a short pad of silica. The solvent was removed at reduced pressure to afford 3-benzyl-2-piperidone (240 mg, 96%) as a white crystalline solid. Chiral HPLC analysis (Chiralpak AS, 60% heptane, 39.2% isopropanol, 0.4% trifluoroacetic acid, 0.4% n-hexylamine, 40° C.) indicated that conversion was 100% and the enantiomeric excess was 83%. 13C NMR: δ 20.10, 24.33, 36.42, 41.31, 41.74, 125.11, 127.32, 128.21, 138.84, 173.69; the preparation of I where n=2 and R1=phenyl In a nitrogen-filled glove box the system was flushed 4 times with hydrogen After 18 h the reaction mixture was filtered through a short pad of silica The solvent was removed at reduced pressure

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 2-piperidone (40 g, 0.404 mol) in tetrahydrofuran (800 ml) at 0° C. was added, over a period of 2 hours, n-butyl lithium (2.5 M in hexane, 356 ml, 0.889 mol). The reaction was cooled to -40° C. and a solution of benzyl bromide (48 ml, 0.404 mol) in tetrahydrofuran (200 ml) was added dropwise over a period of 2 hours. The reaction was allowed to warm slowly to room temperature and stirred for 12 hours. Water (100 ml) and saturated aqueous ammonium chloride (100 ml) were added and the aqueous phase separated and extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with brine (200 ml), dried with sodium sulphate and evaporated in vacuo. The resulting solid was recrystallised from toluene to give the desired product as white needles (41.2 g), m.pt. 120°-123° C. Low resolution mass spectroscopy revealed the mass/charge ratio of the parent molecule ion, M+, to be 190 thereby confirming the molecular of the product to be 190. to warm slowly to room temperature the aqueous phase separated extracted with ethyl acetate (3×100 ml) The combined organic phases were washed with brine (200 ml) dried with sodium sulphate evaporated in vacuo The resulting solid was recrystallised from toluene

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

実験手順: A solution of 1,3-diphenylmethyl-2-piperidinone (2.79 g, 10 mmol) in dry THF (25 mL) was added at -78° C. to a well stirred solution of Li metal (0.70 g, 100 mmol) in liquid NH3 (200 mL). After 15 min, the cooling bath was removed, and the NH3 was allowed to escape (ca. 2 h). The resulting colorless residue was treated with saturated NH4Cl (50 mL), and extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine (25 mL), dried over MgSO4, and concentrated in vacuo to give 2.78 g of brown viscous residue. Flash chromatography over silica gel (1% MeOH in CHCl3 -EtOAc, 1:1) afforded the lactam (See: Rodrequez M, Heitz A, Martinez J (1992) supra)(0.87 g, 46% ) as a colorless solid: mp 120-122° C. (CH2Cl2 -hexanes). the cooling bath was removed (ca. 2 h) The resulting colorless residue was treated with saturated NH4Cl (50 mL) extracted with EtOAc (3×50 mL) The combined organic extract was washed with brine (25 mL) dried over MgSO4 concentrated in vacuo