8-bromooct-1-ene

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: 1-(7,8-Dihydroxyoctyl)-3,7-dimethylxanthine was used as an intermediate for the synthesis of inventive compound no. 1514 (example 12). To a suspension of sodium hydride (580 mg, 24.2 mmol) in dimethylsulfoxide (100 ml) was added theobromine (3.96 g, 22.0 mmol). After stirring for 30 min, 8-bromo-1-octene (3.96 g, 22 mmol) was added and the mixture was stirred for 16 hr. The mixture was poured into water (200 ml) and extracted with dichloromethane (3×50 ml). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 ml), dried over sodium sulfate, and the solvent was evaporated under vacuum to give 1-(7-octenyl)-3,7-dimethylxanthine (6.22 g, 97% yield) as an oil which solidified upon standing. the mixture was stirred for 16 hr extracted with dichloromethane (3×50 ml) The combined organic layers were washed with saturated aqueous sodium chloride solution (50 ml) dried over sodium sulfate the solvent was evaporated under vacuum

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

実験手順: Sodium hydride (0.11 g) was added to a solution of 3-azabicyclo[3.1.0]hexane-2,4dione (0.3 g) and 7-octenyl bromide (0.52 g) in dimethylformamide (5 ml) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. The mixture was diluted with water (15 ml) and then extracted with toluene (20 ml). The organic extract was washed with water (15 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg) to give the title compound as a colourless oil. extracted with toluene (20 ml) The organic extract was washed with water (15 ml) dried (MgSO4) evaporated in vacuo The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg)

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

実験手順: Combine sodium imidazole (5 g) and 8-bromo-1-octene (5 g) in DMF and stir overnight. Partition the reaction product between water and dichloromethane, evaporate the organic layer and purify the resultant residue on a silica gel column. Add the imidazole compound (4.6 g) and phenol (1 g) to dichloromethane (250 ml), saturate the solution with HBr gas and stir for 4 hours. Evaporate the solvent and wash the residue with THF: hexane (1:1) to obtain 1-(2-bromooctyl)imidazole hydrobromide. Partition the reaction product between water and dichloromethane evaporate the organic layer purify the resultant residue on a silica gel column Add the imidazole compound (4.6 g) and phenol (1 g) to dichloromethane (250 ml) saturate the solution with HBr gas Evaporate the solvent wash the residue with THF: hexane (1:1)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 250-mL round-bottom flask equipped with a stir bar and a water-jacketed reflux condenser was charged with trimethylsilylacetylene (6.00 mL, 42.0 mmol). THF (50 mL) was added, and the mixture was allowed to cool to 0° C. (ice-bath). nButyllithium (29.0 mL, 42.0 mmol, 1.46 M solution in hexanes) was added dropwise by a syringe, and the ice-bath was removed following the addition. The mixture was allowed to warm to 22° C. as it stirred for 1 h, at which point 8-bromo-1-octene (3.50 mL, 21.0 mmol) was added, and the mixture was allowed to reflux for 12 h. The mixture was allowed to cool to 0° C., quenched by addition of 50 mL water, washed with CH2Cl2 (5×50 mL). The combined organic layers were washed in brine (1×50 mL), dried over MgSO4, filtered, and concentrated in vacuo. The resulting brown oil was filtered through a plug of silica gel (eluted in pentane), the filtrate was concentrated and the resulting brown oil distilled under vacuum (1.0 torr). The resulting yellow oil was re-distilled under vacuum (1.0 ton) to afford dec-9-en-1-ynyltrimethylsilane (0.700 g, 3.40 mmol, 14.0% yield) as a colorless oil. IR (neat): 3078 (w), 2929 (m), 2857 (w), 2175 (m), 1641 (w), 1461 (w), 1325 (w), 1248 (m), 1032 (w), 994 (w), 910 (m), 837 (s), 758 (s), 725 (w), 697 (w), 638 (m), 575 (w), 450 (w); 1H NMR (400 MHz, CDCl3): δ 5.86-5.76 (1H, m), 4.99 (1H, dd, J=17.2, 2.0 Hz), 4.93 (1H, dd, J=10.0,0.8 Hz), 2.21 (2H, t, J. 7.2 Hz), 2.05 (2H, app q, J=7.1 Hz), 1.55-1.48 (2H, m), 1.40-1.28 (6H, m), 0.14 (9H, s); 13C NMR (100 MHz, CDCl3): δ 139.2, 114.4, 107.8, 84.4, 33.9, 28.9, 28.8, 28.7, 28.7, 20.0, 0.3; HRMS (ESI+) [M+H]+ calcd for C13H25Si: 209.1726, found: 209.1719. A 250-mL round-bottom flask equipped with a stir bar and a water-jacketed reflux condenser the ice-bath was removed the addition to warm to 22° C. as it was added to reflux for 12 h to cool to 0° C. quenched by addition of 50 mL water washed with CH2Cl2 (5×50 mL) The combined organic layers were washed in brine (1×50 mL) dried over MgSO4 filtered concentrated in vacuo The resulting brown oil was filtered through a plug of silica gel (eluted in pentane) the filtrate was concentrated the resulting brown oil distilled under vacuum (1.0 torr) The resulting yellow oil was re-distilled under vacuum (1.0 ton)

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

実験手順: Following the general procedure, 8-bromooct-1-ene (50.0 mg, 0.262 mmol) was treated with p-methoxyphenyl vinyl ether (79.0 mg, 0.5 23 mmol) and 1.2 mol % of in situ-generated complex 1a (31.0 μL, 0.10 M, 3.14 μmol; final substrate concentration=8.45 M) and allowed to stir for 16 h. The unpurified product is >98% Z (as determined by 400 MHz 1H NMR analysis). Excess p-methoxyphenyl vinyl ether was removed by vacuum distillation (1.0 torr, 80° C.). The resulting oil was purified by neutral alumina chromatography (100% hexanes to 100:1 hexanes:Et2O) to afford 10b (56.9 mg, 0.182 mmol, 69.0% yield, >98% Z isomer) as a colorless oil. IR (neat): 2924 (s), 2854 (m), 1665 (m), 1503 (s), 1463 (m), 1441 (m), 1389 (w), 1214 (s), 1180 (m), 1102 (m), 1040 (s); 1H NMR (400 MHz, CDCl3): δ 6.95-6.90 (2H, m), 6.86-6.82 (2H, m), 6.28 (1H, dt, J=6.0, 1.5 Hz), 4.73 (1H, td, J=7.4, 6.0 Hz), 3.78 (3H, s), 3.40 (2H, t, J=7.0 Hz), 2.24-2.17 (2H, m), 1.90-1.81 (2H, m), 1.49-1.32 (6H, m); 13C NMR (100 MHz, CDCl3): δ 155.2, 151.8, 141.4, 117.5, 114.8, 112.0, 55.8, 34.1, 33.0, 29.4, 28.4, 28.1, 23.9; HRMS (ESI+) [M+H]+ calcd for C15H22BrO2: 313.0803, found: 313.0800 Excess p-methoxyphenyl vinyl ether was removed by vacuum distillation (1.0 torr, 80° C.) The resulting oil was purified by neutral alumina chromatography (100% hexanes to 100:1 hexanes:Et2O)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium ethoxide (4.98 g) was added to a solution (240 ml) of 2-(4-hydroxyphenyl)ethyl alcohol (8.68 g) in absolute ethanol and the mixture was stirred at 50° C. for 30 minutes. A solution of 7-octenyl bromide (10 g) in anhydrous tetrahydrofuran was dropwise added thereto and the mixture was stirred at 50° C. for 6 hours. The reaction mixture was concentrated, poured into ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled away and the residue was purified by silica gel chromatography (eluent; ethyl acetate:hexane=1:5) to give the subject compound (10.76 g) as an oily substance. the mixture was stirred at 50° C. for 6 hours The reaction mixture was concentrated poured into ice water extracted with ethyl acetate The ethyl acetate layer was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was distilled away the residue was purified by silica gel chromatography (eluent; ethyl acetate:hexane=1:5)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium ethoxide (4.98 g) was added to a solution (240 ml) of 2-(4-hydroxyphenyl)ethyl alcohol (8.68 g) in absolute ethanol and the mixture was stirred at 50° C. for 30 minutes. A solution of 7-octenyl bromide (10 g) in anhydrous tetrahydrofuran was dropwise added thereto and the mixture was stirred at 50° C. for 6 hours. The reaction mixture was concentrated, poured into ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled away and the residue was purified by silica gel chromatography (eluent; ethyl acetate:hexane=1:5) to give the subject compound (10.76 g) as an oily substance. the mixture was stirred at 50° C. for 6 hours The reaction mixture was concentrated poured into ice water extracted with ethyl acetate The ethyl acetate layer was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was distilled away the residue was purified by silica gel chromatography (eluent; ethyl acetate:hexane=1:5)

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

実験手順: 8-Iodooct-1-ene was prepared by refluxing 5 g of 8-bromooct-1-ene (26 mmol) and 10 g of sodium iodide in 50 ml of acetone for 1 hour. The acetone was stripped and the residue was partitioned between water and ether. The aqueous phase was washed with brine, dried over magnesium sulfate and stripped to give 5.66 g of 8-iodooct-1-ene. 8-Iodooct-1-ene was prepared the residue was partitioned between water and ether The aqueous phase was washed with brine dried over magnesium sulfate

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium ethoxide (4.98 g) was added to a solution (240 ml) of 2-(4-hydroxyphenyl)ethyl alcohol (8.68 g) in absolute ethanol and the mixture was stirred at 50° C. for 30 minutes. A solution of 7-octenyl bromide (10 g) in anhydrous tetrahydrofuran was dropwise added thereto and the mixture was stirred at 50° C. for 6 hours. The reaction mixture was concentrated, poured into ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled away and the residue was purified by silica gel chromatography (eluent; ethyl acetate:hexane=1:5) to give the subject compound (10.76 g) as an oily substance. the mixture was stirred at 50° C. for 6 hours The reaction mixture was concentrated poured into ice water extracted with ethyl acetate The ethyl acetate layer was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was distilled away the residue was purified by silica gel chromatography (eluent; ethyl acetate:hexane=1:5)