1,2-二溴-4-氟-3-碘苯

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A thick-walled glass vessel was charged with 1,2-dibromo-4-fluoro-3-iodobenzene (8.31 g, 21.88 mmol), Pd(PPh3)2Cl2 (0.768 g, 1.094 mmol), and CuI (0.292 g, 1.532 mmol) and sealed with a rubber septum. Anhyd THF (30 mL) and DIPA (30.8 mL, 219 mmol) were added via syringe and the mixture was degassed 10 min by sparging with N2 while immersed in an ultrasonic bath. Ethynyltrimethylsilane (3.40 mL, 24.07 mmol) was added via syringe and the septum was replaced with a PTFE bushing. The mixture was stirred in an oil bath at 40° C. After 40 h, the mixture was cooled, diluted with EtOAc and filtered through a pad of Celite. The filtrate was washed (satd NH4Cl×2, water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution) affording ((2,3-dibromo-6-fluorophenyl)ethynyl)trimethylsilane (6.08 g, 17.37 mmol, 79% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.53 (dd, J=8.9, 5.4 Hz, 1H), 6.95 (dd, J=8.9, 8.1 Hz, 1H), 0.29 (s, 9H); MS (GCMS EI) m/z 348 ([M]+, Br isotopes, 18%), 350 ([M]+, Br isotopes, 34%), 352 ([M]+, Br isotopes, 18%), 333 ([M-CH3]+, Br isotopes, 56%), 335 ([M-CH3]+, Br isotopes, 100%), 337 ([M-CH3]+, Br isotopes, 54%). sealed with a rubber septum the mixture was degassed 10 min by sparging with N2 while immersed in an ultrasonic bath the mixture was cooled filtered through a pad of Celite The filtrate was washed (satd NH4Cl×2, water, brine) dried over Na2SO4 concentrated in vacuo The residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution)

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

实验步骤: To a solution of freshly-prepared LDA (33.9 mmol) in anhyd THF (100 mL) at −78° C. was added a solution of 1,2-dibromo-4-fluorobenzene (4 mL, 32.3 mmol) in THF (8 mL), dropwise at such a rate that the internal temperature remained <−70° C. The mixture was stirred 30 min and iodine (9.02 g, 35.5 mmol) was added in one portion. The mixture was stirred 30 min, quenched by addition of 10% Na2S2O3, and removed from the cooling bath. Upon warming the mixture was poured into water and extracted with EtOAc (×3). Combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was eluted from a pad of silica (hexanes→2% EtOAc/hexanes) and recrystallized from MeOH-water affording 1,2-dibromo-4-fluoro-3-iodobenzene (8.59 g, 70% yield) as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J=8.8, 5.5 Hz, 1H), 6.93 (dd, J=8.8, 7.0 Hz, 1H); MS (GCMS EI) m/z 378 ([M]+, Br isotopes, 56%), 380 ([M]+, Br isotopes, 100%), 382 ([M]+, Br isotopes, 51%). remained <−70° C The mixture was stirred 30 min quenched by addition of 10% Na2S2O3 removed from the cooling bath Upon warming the mixture was poured into water extracted with EtOAc (×3) Combined organics were washed (water, brine) dried over Na2SO4 concentrated in vacuo The residue was eluted from a pad of silica (hexanes→2% EtOAc/hexanes) recrystallized from MeOH-water