十一碳-4-烯

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution comprising 2-naphth-2-ylethanol (0.5 g, 2.9 mmol) in dry DMF (5 mL) was combined under nitrogen with diphenylphosphoryl azide (0.74 mL, 3.42 mmol) and 1,8-diazaabicyclo[5.4.0]undec-7-ene (0.47 mL. 3.14 mmol). The mixture was heated at 65° C. for 3 hours and then partitioned between water and diethyl ether. The aqueous layer was separated and extracted with diethyl ether. The combined organic layers were washed with 3N hydrochloric acid and then saturated sodium bicarbonate, dried (MgSO4), filtered and concentrated by rotary evaporation. The residue was dissolved in THF (5 mL) and the solution was combined with triphenylphosphine (1 g, 3.81 mmol), stirred for 2 hours at room temperature, diluted with water (0.100 mL), stirred 3 hours, diluted with concentrated hydrochloric acid (0.33 mL) to give a precipitate, treated with ethanol (5 mL) to dissolve the precipitate and treated with diethyl ether, added slowly, to give a white precipitate. The while precipitate was isolated by filtration, washed with diethyl ether and dried under vacuum to provide 2-naphth-2-ylethylamine hydrochloride (0.447 g, 75% yield); partitioned between water and diethyl ether The aqueous layer was separated extracted with diethyl ether The combined organic layers were washed with 3N hydrochloric acid saturated sodium bicarbonate, dried (MgSO4) filtered concentrated by rotary evaporation The residue was dissolved in THF (5 mL) stirred 3 hours to give a precipitate to dissolve the precipitate added slowly to give a white precipitate The while precipitate was isolated by filtration washed with diethyl ether dried under vacuum

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 5-iodo-2-aminobenzaldehyde (24.0 g, 96.7 mmol), diazbicyclo[2.2.2]-undec-7-ene (32.2 g, 212.0 mmol), and ethyl 4,4,4-trifluorocrotonate (35.7 g, 212.0 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (48 mL) was heated at 60° C. for 8 hours. The solution was cooled to room temperature and the solution poured into ethyl acetate-hexanes (1:1, 500 mL). The solution was extracted with 2.5 N aqueous hydrochloric acid (2×200 mL), saturated aqueous ammonium chloride (2×200 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The resulting dark yellow oil was dissolved in hexanes (100 mL) and fine yellow crystals formed upon standing. Vacuum filtration of this suspension yielded ethyl 6-iodo-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate as fine yellow crystals (19.3 g, 50% yield): mp 137-138° C. 1H NMR (CDCl3, 300 MHz) 7.62 (s, 1H), 7.36-7.48 (m, 2H), 6.43 (d, J=8.2 Hz), 5.36 (brs, 1H), 5.11 (q, 1H, J=7.1 Hz), 4.25-4.35 (m, 2H), 1.34 (t, 3H, J=7.0 Hz). ESHRMS m/z 395.9716 (M−H, Calc'd 395.9708). The solution was cooled to room temperature The solution was extracted with 2.5 N aqueous hydrochloric acid (2×200 mL), saturated aqueous ammonium chloride (2×200 mL) dried over sodium sulfate filtered concentrated in vacuo The resulting dark yellow oil was dissolved in hexanes (100 mL) fine yellow crystals formed Vacuum filtration of this suspension

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

实验步骤: To a solution of 1H-indole-4-methanol (71 mg, 0.48 mmol) in tetrahydrofuran (1 mL) at 0° C. was added diphenylphosphoryl azide (156 μL, 0.72 mmol) followed by 1,8-diaza[5.4.0]undec-7-ene (87.4 μL, 0.58 mmol). The cooling bath was removed and the solution was allowed to stir for 5 h. The solvent was evaporated and ethyl acetate was added. The solution was washed with 1 M HCl and brine, dried (MgSO4), filtered, concentrated and chromatographed (12% ethyl acetate/hexanes) to give 4-(azidomethyl)-1H-indole (1.496 g, 88%) as an oil. The cooling bath was removed The solvent was evaporated ethyl acetate was added The solution was washed with 1 M HCl and brine dried (MgSO4) filtered concentrated chromatographed (12% ethyl acetate/hexanes)

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

实验步骤: A mixture of 2,6-dibromopyridine (2.37 g, 0.01 mol), pyrrolidin-3-ol (1.0 g, 0.01 mol), 1,8-diazabicclo[5.4.0)-7-undecene (1.5 mL) in 10 mL of THF was heated at 70° C. under a nitrogen atmosphere for 11 hours. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate (30 mL). The resulting solution was washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (10-30% ethyl acetate/hexane) to give the title compound. The resulting solution was washed with water and brine dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by silica gel chromatography (10-30% ethyl acetate/hexane)

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

实验步骤: To a 50 mL round-bottomed flask equipped with a magnetic stirbar was added 3-furan methanol (1.00 g, 10.2 mmol) and a solution of diphenyl phosphoryl azide (3.37 g, 12.2 mmol) in toluene (30 mL). The stirring solution is allowed to cool to 0° C., in which 1, 8 Diazabycyclo [5.4.0.]undec-7-ene (1.86 g, 12.2 mmol) was added dropwise. The reaction is allowed to slowly warm to ambient temperature for an additional 16 hours of stirring. After this period, the reaction mixture is washed with water (2×20 mL) and then with 5% HCl (20 mL). Volatiles are evaporated under reduced pressure. The resulting residue is then purified by column chromatography (1:9 ethyl acetate/hexane) providing 3-azidomethyl furan (1.19 g, 95%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.46 (d, 1H), δ 7.44 (s, 1H), δ 6.42 (d, 1H), δ 4.20 (s, 2H). ppm; 13C NMR (75 MHz, CDCl3) δ 144.1, 141.1, 110.4, 92.1, 45.8 ppm; LRMS (EI) Calcd for C5H5N3O (M+) 123, found 123. To a 50 mL round-bottomed flask equipped with a magnetic stirbar was added dropwise After this period the reaction mixture is washed with water (2×20 mL) Volatiles are evaporated under reduced pressure The resulting residue is then purified by column chromatography (1:9 ethyl acetate/hexane)

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-pyridinecarboxaldehyde (1.2 mL, 1.2 mM) and 2,5-dimethyl-2-phenyl-3(2H)-furanone (1.5 g, 8 mM) in ethanol (15 mL), was added 1,8-diazebicyclo[4.5.0]undec-7ene (DBU, 0.2 mL, 1.3 mM). The reaction solution was heated at 80° C. for 5 hours. After the reaction solution cooled to room temperature, saturated aqueous sodium chloride (400 mL) was added. The aqueous layer was extracted with dichloromethane (3×100 mL). The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL), dried over MgSO4, filtered and concentrated to give a yellow solid. Purification by trituration with 10% diethyl ether in hexane gave a pale pink solid (887 mg, 40% yield), m.p. 74.5°-76° C. After the reaction solution cooled to room temperature The aqueous layer was extracted with dichloromethane (3×100 mL) The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL) dried over MgSO4 filtered concentrated to give a yellow solid Purification by trituration with 10% diethyl ether in hexane

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

实验步骤: 2(b) 314 μl of 1,8-diaza[5.4.0]-7-undecene were added to a solution of 620 mg of diethyl 2-(3-bromopropionamido)malonate (prepared as described above) dissolved in methylene chloride, and the mixture was stirred at room temperature for 3 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, poured into water and then extracted with diethyl ether. The extract was washed with 5% w/v aqueous hydrochloric acid, with a 5% w/v aqueous solution of sodium bicarbonate and with water, in that order, and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, to give a crude product. This was purified by column chromatography through silica gel, eluted with a 2:1 by volume mixture of cyclohexane and ethyl acetate, to give 171 mg of diethyl 2-oxopyrrolidine-5,5-dicarboxylate. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure poured into water extracted with diethyl ether The extract was washed with 5% w/v aqueous hydrochloric acid, with a 5% w/v aqueous solution of sodium bicarbonate and with water, in that order dried over anhydrous magnesium sulfate The solvent was then removed by distillation under reduced pressure to give a crude product This was purified by column chromatography through silica gel eluted with a 2:1 by volume mixture of cyclohexane and ethyl acetate

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

实验步骤: 2(b) 314 μl of 1,8-diaza[5.4.0]-7-undecene were added to a solution of 620 mg of diethyl 2-(3-bromopropionamido)malonate (prepared as described above) dissolved in methylene chloride, and the mixture was stirred at room temperature for 3 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, poured into water and then extracted with diethyl ether. The extract was washed with 5% w/v aqueous hydrochloric acid, with a 5% w/v aqueous solution of sodium bicarbonate and with water, in that order, and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, to give a crude product. This was purified by column chromatography through silica gel, eluted with a 2:1 by volume mixture of cyclohexane and ethyl acetate, to give 171 mg of diethyl 2-oxopyrrolidine-5,5-dicarboxylate. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure poured into water extracted with diethyl ether The extract was washed with 5% w/v aqueous hydrochloric acid, with a 5% w/v aqueous solution of sodium bicarbonate and with water, in that order dried over anhydrous magnesium sulfate The solvent was then removed by distillation under reduced pressure to give a crude product This was purified by column chromatography through silica gel eluted with a 2:1 by volume mixture of cyclohexane and ethyl acetate

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-pyridinecarboxaldehyde (1.2 mL, 1.2 mM) and 2,5-dimethyl-2-phenyl-3(2H)-furanone (1.5 g, 8 mM) in ethanol (15 mL), was added 1,8-diazebicyclo[4.5.0]undec-7-ene (DBU, 0.2 mL, 1.3 mM). The reaction solution was heated at 80° C. for 5 hours. After the reaction solution cooled to room temperature, saturated aqueous sodium chloride (400 mL) was added. The aqueous layer was extracted with dichloromethane (3×100 mL). The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL), dried over MgSO4, filtered and concentrated to give a yellow solid. Purification by trituration with 10% diethyl ether in hexane gave a pale pink solid (887 mg, 40% yield), m.p. 74.5°-76° C. After the reaction solution cooled to room temperature The aqueous layer was extracted with dichloromethane (3×100 mL) The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL) dried over MgSO4 filtered concentrated to give a yellow solid Purification by trituration with 10% diethyl ether in hexane

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-pyridinecarboxaldehyde (1.2 mL, 1.2 mM) and 2,5-dimethyl-2-phenyl-3(2H)-furanone (1.5 g, 8 mM) in ethanol (15 mL), was added 1,8-diazebicyclo[4.5.0]undec-7-ene (DBU, 0.2 mL, 1.3 mM). The reaction solution was heated at 80° C. for 5 hours. After the reaction solution cooled to room temperature, saturated aqueous sodium chloride (400 mL) was added. The aqueous layer was extracted with dichloromethane (3×100 mL). The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL), dried over MgSO4, filtered and concentrated to give a yellow solid. Purification by trituration with 10% diethyl ether in hexane gave a pale pink solid (887 mg, 40% yield), m.p. 74.5°-76° C. After the reaction solution cooled to room temperature The aqueous layer was extracted with dichloromethane (3×100 mL) The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL) dried over MgSO4 filtered concentrated to give a yellow solid Purification by trituration with 10% diethyl ether in hexane

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-pyridinecarboxaldehyde (1.2 mL, 1.2 mM) and 2,5-dimethyl-2-phenyl-3(2H)-furanone (1.5 g, 8 mM) in ethanol (15 mL), was added 1,8-diazebicyclo[4.5.0]undec-7-ene (DBU, 0.2 mL, 1.3 mM). The reaction solution was heated at 80° C. for 5 hours. After the reaction solution cooled to room temperature, saturated aqueous sodium chloride (400 mL) was added. The aqueous layer was extracted with dichloromethane (3×100 mL). The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL), dried over MgSO4, filtered and concentrated to give a yellow solid. Purification by trituration with 10% diethyl ether in hexane gave a pale pink solid (887 mg, 40% yield), m.p. 74.5°-76° C. After the reaction solution cooled to room temperature The aqueous layer was extracted with dichloromethane (3×100 mL) The combined dichloromethane extracts were washed with saturated aqueous sodium chloride (50 mL) dried over MgSO4 filtered concentrated to give a yellow solid Purification by trituration with 10% diethyl ether in hexane

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

实验步骤: N,N′-carbonyldiimidazole (65.09 g) was added all at once to a solution (200 ml) of N,N-dimethylformamide containing 3-acetylamino-4-nitrobenzoic acid (60.22 g), and the reaction mixture was stirred at room temperature for 1 hour. 1-pentanesulfonamide (60.72 g) and 1,8-diazabicycle[5.4.0]undec-7-ene (61.12 g) were added thereto, and the mixture was stirred at 100° C. for 16 hours. The solvent was evaporated at 90° C. under reduced pressure using a vacuum pump. Chloroform and water were added to the resulting residue, and the pH of the aqueous layer was adjusted to 4 with diluted hydrochloric acid with stirring. The organic layer was separated, dried over sodium sulfate, and then concentrated to yield partially purified N-(n-pentanesulfonyl)-3-(acetylamino)-4-nitrobenzamide. The product was used immediately in the next reaction step. the mixture was stirred at 100° C. for 16 hours The solvent was evaporated at 90° C. under reduced pressure Chloroform and water were added to the resulting residue with stirring The organic layer was separated dried over sodium sulfate concentrated