反应详情

温度

60 °C

THF (5 volumes) and zinc dust (2.4 eq) were charged to a round bottom flask under nitrogen. The slurry was heated to 60° C. and held for 15 min. 1,2-Dibromoethane (0.2 eq) was added and the mixture agitated at 60° C. for 30 min. The mixture was cooled to ambient temperature before 0.4 eq. chlorotrimethylsilane was added. 3-Chloro-2-fluorobenzylbromide (2.0 eq) dissolved in THF was added over 2 h at 0° C. Agitation was stopped and the mixture allowed to settle overnight to give 7 as a solution in THF. Next, 0.16 eq Pd2dba3 and 0.35 eq. triphenylphosphine were charged to a separate flask under argon. THF (10 volumes) and 1-bromo-2,4-dimethoxybenzene were added followed by the solution of compound 7 prepared above. The mixture was heated to 65° C. and agitated overnight. The mixture was cooled to room temperature and quenched with aqueous NH4OH. The organic phase was purified by column chromatography to yield compound 5: 1H NMR (400 MHz, CDCl3): δ 7.33 (td, 1H, J=7, 2 Hz), 7.07-6.99 (m, 2H), 6.91 (d, 1H, J=8 Hz), 6.49 (d, 1H, J=8 Hz), 6.40 (dd, 1H, J=8, 2 Hz), 3.80 (s, 2H), 3.68 (s, 3H), 3.67 (s, 3H).

1. additionwas added
2. additionwas added over 2 h at 0° C
3. waitto settle overnight
4. customprepared above
5. temperatureThe mixture was heated to 65° C.
6. stirringagitated overnight
7. temperatureThe mixture was cooled to room temperature
8. customquenched with aqueous NH4OH
9. customThe organic phase was purified by column chromatography