(2-氧代-2-苯乙基)膦酸二乙酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup. the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL) The organic layer was washed with saturated aq. brine (60 mL) dried (sodium sulfate) decanted evaporated The crude product was purified by FC eluting with 15-20% ethyl acetate in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup. the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL) The organic layer was washed with saturated aq. brine (60 mL) dried (sodium sulfate) decanted evaporated The crude product was purified by FC eluting with 15-20% ethyl acetate in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup. the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL) The organic layer was washed with saturated aq. brine (60 mL) dried (sodium sulfate) decanted evaporated The crude product was purified by FC eluting with 15-20% ethyl acetate in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup. the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL) The organic layer was washed with saturated aq. brine (60 mL) dried (sodium sulfate) decanted evaporated The crude product was purified by FC eluting with 15-20% ethyl acetate in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.255 mL, 301 mg, 1.17 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 45 mg, 1.13 mmol) in THF (7 mL) at rt. After 15 min, a portion (1.8 mL) of the clear solution was removed and discarded, and the remainder cooled in an ice bath. 1-(tert-Butoxycarbonyl)-4-piperidinecarboxaldehyde (177 mg, 0.830 mmol, from Step B) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. After 16 h at rt, the mixture was then partitioned between ether (40 mL) and 2.5 N aq. NaOH (20 mL). The organic layer was washed with sat'd NaCl (20 mL), dried (Na2SO4), decanted, and evaporated. The crude product was purified by flash column chromatography on silica gel, eluting with 10% EtOAc in hexane, to give 201 mg of 1-(tert-butoxycarbonyl)-4-(3-oxo-3-phenylprop-1-enyl)piperidine as a colorless oil. Hydrogenation of this material using 5% Pd/C in 95% ethanol at atmospheric pressure yielded the title compound as a white crystalline solid. a portion (1.8 mL) of the clear solution was removed the remainder cooled in an ice bath for rinsing After 16 h at rt the mixture was then partitioned between ether (40 mL) and 2.5 N aq. NaOH (20 mL) The organic layer was washed with sat'd NaCl (20 mL) dried (Na2SO4) decanted evaporated The crude product was purified by flash column chromatography on silica gel eluting with 10% EtOAc in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup. the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL) The organic layer was washed with saturated aq. brine (60 mL) dried (sodium sulfate) decanted evaporated The crude product was purified by FC eluting with 15-20% ethyl acetate in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL,1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at RT, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to RT. The mixure was then partitioned between ether (120 ml) and 2.5 N NaOH (60 mL). The organic layer was washed with saturated aq. NaCl (60 mL), dried (Na2SO4), decanted, and evaporated. The crude product was purified by flash column chromatography on silica gel eluting with 85:15 v/v to 80:20 v/v hexanes/EtOAc to give 0-95 g of the title compound as a colorless syrup: 1H NMR (400 MHz) δ 7.82 (d, J=8, 21), 7.57 (t, J=8, 1H), 7.48 (t, J=8, 2H), 7.39-7.29 (m, 51), 6.99 (dd, J=15, 6, 1H), 6.87 (dd, J=15, 1, 1H), 5.15 (s, 2H), 2.97-2.82 (m, 2H), 2.50-2.39 (m, 1H), 1.89-1.77 (m, 2H), 1.54-1.39 (m, 2H); ESI-MS 367 (M+NH3+H). the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixure was then partitioned between ether (120 ml) and 2.5 N NaOH (60 mL) The organic layer was washed with saturated aq. NaCl (60 mL) dried (Na2SO4) decanted evaporated The crude product was purified by flash column chromatography on silica gel eluting with 85:15 v/v to 80:20 v/v hexanes/EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup. the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL) The organic layer was washed with saturated aq. brine (60 mL) dried (sodium sulfate) decanted evaporated The crude product was purified by FC eluting with 15-20% ethyl acetate in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup. the clear solution was cooled in an ice bath for rinsing was continued for a total of 2 h The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL) The organic layer was washed with saturated aq. brine (60 mL) dried (sodium sulfate) decanted evaporated The crude product was purified by FC eluting with 15-20% ethyl acetate in hexane