(2-溴-5-碘苯基)甲氧基-叔-butyl-二甲基硅烷

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

实验步骤: To a solution of (2-bromo-5-iodobenzyloxy)-(tert-butyl)dimethylsilane (8.7 g, 20.3 mmol) in tetrahydrofuran (135 mL) under argon at −20° C. was added i-propylmagnesium chloride-lithium chloride solution (1.3M in THF, 16.4 mL, 21.3 mmol). After stirring at this temperature for thirty minutes, a solution of 2-chloro-N-methoxy-N-methyl acetamide (3.4 g, 24.3 mmol) in tetrahydrofuran (5 mL) was added to the reaction via cannula. The reaction was stirred at −20° C. for one hour and then warmed to room temperature. After one hour at room temperature the reaction was diluted with ethyl acetate and the organics were washed with saturated aqueous NH4Cl solution, water and brine. The organic layer was dried (MgSO4) and concentrated, and the resulting residue was purified by flash chromatography to yield 1-(4-bromo-3-((tert-butyldimethylsilyloxy)methyl)phenyl)-2-chloroethanone (5.1 g, 67%). The reaction was stirred at −20° C. for one hour the organics were washed with saturated aqueous NH4Cl solution, water and brine The organic layer was dried (MgSO4) concentrated the resulting residue was purified by flash chromatography

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

实验步骤: To a solution of 2-bromo-5-iodobenzoic acid (11.4 g, 34.8 mmol) in dichloromethane (140 mL) was added methanol (17 mL) followed by trimethylsilyldiazomethane solution (2M in hexanes, 19.2 mL, 38.4 mmol). The reaction was stirred at room temperature for twelve hours, quenched by the dropwise addition of acetic acid (5 mL) and thoroughly concentrated. The resulting residue was dissolved in tetrahydrofuran. To this solution was added diisobutylaluminum hydride solution (1M in DCM, 50 mL, 50 mmol) and the reaction was stirred at room temperature. After sixteen hours, more diisobutylaluminum hydride solution (1M in DCM, 50 mL, 50 mmol) was added. After 96 more hours at room temperature the reaction was diluted with ether (100 mL) and quenched by the sequential addition of water (4 mL), 15% aqueous NaOH solution (4 mL) and water (10 mL). After thirty minutes the mixture was filtered through Celite and the filtrate was concentrated. The resulting residue was dissolved in dimethylformamide (75 mL). To this solution was added imidazole (6.1 g, 89.6 mmol) and t-butyldimethylchlorosilane (6.8 g, 45.1 mmol). The reaction was stirred at room temperature for two hours and then diluted with ethyl acetate. The organics were washed with saturated aqueous NH4Cl solution, water and brine. The organic layer was dried (MgSO4) and concentrated, and the resulting residue was purified by flash column chromatography to yield (2-bromo-5-iodobenzyloxy)-(tert-butyl)dimethylsilane (9.2 g, 62%). quenched by the dropwise addition of acetic acid (5 mL) thoroughly concentrated The resulting residue was dissolved in tetrahydrofuran the reaction was stirred at room temperature After sixteen hours quenched by the sequential addition of water (4 mL), 15% aqueous NaOH solution (4 mL) and water (10 mL) After thirty minutes the mixture was filtered through Celite the filtrate was concentrated The resulting residue was dissolved in dimethylformamide (75 mL) The reaction was stirred at room temperature for two hours The organics were washed with saturated aqueous NH4Cl solution, water and brine The organic layer was dried (MgSO4) concentrated the resulting residue was purified by flash column chromatography