N-diazomethanesulfonamide

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

実験手順: To a solution of 5.80 g (25.1 mmol) of methyl 3-(2-chloro-6-fluorophenyl)-3-oxopropionate in 60 mL acetonitrile was added 3.9 mL (28 mmol) of triethylamine followed by 3.05 g (25.2 mmol) of methanesulfonyl azide. The mixture was stirred at room temperature for 18 h and concentrated by rotary evaporation. The resulting solid mass was washed with ethyl acetate/hexanes and the washings were filtered through a plug of silica gel. The filtrate was concentrated to give 4.90 g (76%) of the title compound as a light yellow solid. concentrated by rotary evaporation The resulting solid mass was washed with ethyl acetate/hexanes the washings were filtered through a plug of silica gel The filtrate was concentrated

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

実験手順: To an ice-cooled solution of sodium hydride in dry toluene, (2-oxo-propyl)-phosphonic acid dimethyl ester was added slowly. The solution mixture was stirred for 1 hour. Methanesulfonyl azide, prepared by the reaction of methanesulfonyl chloride and sodium azide, dissolved in dry toluene and dry tetrahydrofuran was added to a solution. The mixture was allowed to slowly warm up to the ambient temperature and stirred for additional 2 hours. Filtration through a celite filter cake gave yellowish oil of (1-Diazo-2-oxo-propyl)-phosphonic acid dimethyl ester, which was used for the next step without any further purification. was added slowly stirred for additional 2 hours Filtration through a celite filter cake

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

実験手順: To a solution of tert-butyl 4-methoxy-4-(1,3-dioxopent-1-yl)piperidine-1-carboxylate (0.227 g, 0.724 mmol) from Step C in dichloromethane (10 mL) was added triethylamine (0.101 mL, 0.724 mmol). Next, a solution of mesyl azide (0.087 g, 0.724 mmol) in dichloromethane (1 mL) was added. The reaction mixture was stirred for 3.5 h at room temperature. Additional mesyl azide (0.026 g, 0.217 mmol) was added. After 2 h, the reaction mixture was diluted with dichloromethane, poured into 1N sodium hydroxide solution, and extracted three times with dichloromethane. The organic layers were combined, washed with saturated sodium chloride, dried over sodium sulfite, filtered, and concentrated. The residue was purified by flash chromatography eluting with 5% ethyl acetate/dichloromethane to afford the title compound (0.174 g). MS/EI (acetonitrile/water): m/z 362 (M+Na) retention time=3.37 min. After 2 h extracted three times with dichloromethane washed with saturated sodium chloride dried over sodium sulfite filtered concentrated The residue was purified by flash chromatography eluting with 5% ethyl acetate/dichloromethane

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

実験手順: To a solution of tert-butyl 4-methoxy-4-(1,3-dioxopent-1-yl)piperidine-1-carboxylate (0.227 g, 0.724 mmol) from Step C in dichloromethane (10 mL) was added triethylamine (0.101 mL, 0.724 mmol). Next, a solution of mesyl azide (0.087 g, 0.724 mmol) in dichloromethane (1 mL) was added. The reaction mixture was stirred for 3.5 h at room temperature. Additional mesyl azide (0.026 g, 0.217 mmol) was added. After 2 h, the reaction mixture was diluted with dichloromethane, poured into 1N sodium hydroxide solution, and extracted three times with dichloromethane. The organic layers were combined, washed with saturated sodium chloride, dried over sodium sulfite, filtered, and concentrated. The residue was purified by flash chromatography eluting with 5% ethyl acetate/dichloromethane to afford the title compound (0.174 g). MS/EI (acetonitrile/water): m/z 362 (M+Na) retention time=3.37 min. After 2 h extracted three times with dichloromethane washed with saturated sodium chloride dried over sodium sulfite filtered concentrated The residue was purified by flash chromatography eluting with 5% ethyl acetate/dichloromethane

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

実験手順: β-ketoamide 13 (3.70 g, 7.80 mmol, 1.0 equiv) was dissolved in 20.0 mL of acetonitrile (0.37 M) and H2O (0.14 mL, 1.0 equiv). Diazo transfer reagent, MeSO2N3 (1.02 mL, 11.70mmol, 1.5 equiv) and 1,8-Diazabicyclo[5.4.0]undec-7-ene (1.75 mL, 11.70 mmol, 1.5 equiv) were sequentially added. The resulting reaction mixture was permitted to stir for 4 h and then this reaction mixture was diluted with diethyl ether. The organic phase was washed sequentially with 10% NaOH, water, and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and then concentrated in vacuo. The oil was diluted in 1/1 ethyl acetate/hexanes and loaded onto a small plug of silica. The plug was eluted with 1/1 ethyl acetate/hexanes and the organics concentrated to provide the pure product 14 as a pale yellow foam (3.67 g) representing a 94% yield. X-ray quality crystals were grown from EtOAc/hexanes. m.p.=130-131° C.; [α]D27=−68.4° (c=4.3, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.47-7.49 (m, 6H); 7.19-7.22 (m, 6H), 7.13 (tt, J=1.6, 7.3 Hz, 3H), 4.88 (dt, J=5.7, 11.1 Hz, 1H), 3.68 (s, 3H); 3.60 (s, 3H); 3.11 (s, 3H), 2.74 (dd, J=6.1, 13.8 Hz, 1H); 2.61 (dd, J=6.1, 13.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 193.74, 161.01, 145.24, 128.04, 126.72, 125.31, 70.06, 60.18, 55.19, 50.77, 39.07, 32.65; IR (thin film): 3057, 2948, 2118, 1736, 1638, 1596, 1490, 1461, 1447, 1373, 1267, 1192, 1162, 1113, 1028, 940, 904, 776, 736, 706, 644 cm−1; HRMS [M+Na] for C28H28N4O5Na, calcd., 523.19519, found, 523.19997 (Error=9.1333 ppm). The resulting reaction mixture The organic phase was washed sequentially with 10% NaOH, water, and brine The organic phase was dried over anhydrous magnesium sulfate filtered concentrated in vacuo The oil was diluted in 1/1 ethyl acetate/hexanes The plug was eluted with 1/1 ethyl acetate/hexanes the organics concentrated

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

実験手順: To an ice-cooled solution of sodium hydride in dry toluene, (2-oxo-propyl)-phosphonic acid dimethyl ester was added slowly. The solution mixture was stirred for 1 hour. Methanesulfonyl azide, prepared by the reaction of methanesulfonyl chloride and sodium azide, dissolved in dry toluene and dry tetrahydrofuran was added to a solution. The mixture was allowed to slowly warm up to the ambient temperature and stirred for additional 2 hours. Filtration through a celite filter cake gave yellowish oil of (1-Diazo-2-oxo-propyl)-phosphonic acid dimethyl ester, which was used for the next step without any further purification. was added slowly stirred for additional 2 hours Filtration through a celite filter cake

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

実験手順: To a solution of 5.80 g (25.1 mmol) of methyl 3-(2-chloro-6-fluorophenyl)-3-oxopropionate in 60 mL acetonitrile was added 3.9 mL (28 mmol) of triethylamine followed by 3.05 g (25.2 mmol) of methanesulfonyl azide. The mixture was stirred at room temperature for 18 h and concentrated by rotary evaporation. The resulting solid mass was washed with ethyl acetate/hexanes and the washings were filtered through a plug of silica gel. The filtrate was concentrated to give 4.90 g (76%) of the title compound as a light yellow solid. concentrated by rotary evaporation The resulting solid mass was washed with ethyl acetate/hexanes the washings were filtered through a plug of silica gel The filtrate was concentrated

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

実験手順: To an ice-cooled solution of sodium hydride in dry toluene, (2-oxo-propyl)-phosphonic acid dimethyl ester was added slowly. The solution mixture was stirred for 1 hour. Methanesulfonyl azide, prepared by the reaction of methanesulfonyl chloride and sodium azide, dissolved in dry toluene and dry tetrahydrofuran was added to a solution. The mixture was allowed to slowly warm up to the ambient temperature and stirred for additional 2 hours. Filtration through a celite filter cake gave yellowish oil of (1-Diazo-2-oxo-propyl)-phosphonic acid dimethyl ester, which was used for the next step without any further purification. was added slowly stirred for additional 2 hours Filtration through a celite filter cake

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

実験手順: To a solution of tert-butyl 4-methoxy-4-(1,3-dioxopent-1-yl)piperidine-1-carboxylate (0.227 g, 0.724 mmol) from Step C in dichloromethane (10 mL) was added triethylamine (0.101 mL, 0.724 mmol). Next, a solution of mesyl azide (0.087 g, 0.724 mmol) in dichloromethane (1 mL) was added. The reaction mixture was stirred for 3.5 h at room temperature. Additional mesyl azide (0.026 g, 0.217 mmol) was added. After 2 h, the reaction mixture was diluted with dichloromethane, poured into 1N sodium hydroxide solution, and extracted three times with dichloromethane. The organic layers were combined, washed with saturated sodium chloride, dried over sodium sulfite, filtered, and concentrated. The residue was purified by flash chromatography eluting with 5% ethyl acetate/dichloromethane to afford the title compound (0.174 g). MS/EI (acetonitrile/water): m/z 362 (M+Na) retention time=3.37 min. After 2 h extracted three times with dichloromethane washed with saturated sodium chloride dried over sodium sulfite filtered concentrated The residue was purified by flash chromatography eluting with 5% ethyl acetate/dichloromethane