反应详情

温度

-40 °C

To a solution of 1-ethoxy-4-fluorobenzene (1.1 g, 7.9 mmol) and pentamethyl diethylene triamine (2 mL) in anhydrous THF (6 mL) was added BuLi dropwise (1.38 M, 5.98 mL, 8.3 mmol) at −78° C. After addition, the reaction mixture was warmed up to −40° C. and stirred for 30 min, the reaction mixture was then cooled to −78° C. and DMF (0.7 mL) was added. The solution was warmed to rt, and stirred for 1 h. The reaction mixture was then partitioned between EtOAc and sat. NH4Cl, the organic layer was dried over (Na2SO4), filtered and concentrated. The residue was subjected to chromatographic purification (0-10% EtOAc/hexanes gradient), 600 mg (55%) of Intermediate 53.1 was obtained. 1H NMR (CDCl3) δ 1.40 (t, 3H), 4.08 (q, 2H), 6.81 (m, 1H), 7.15 (m, 1H), 7.29 (m, 1H), 10.33 (s, 1H).

1. additionAfter addition
2. temperaturethe reaction mixture was then cooled to −78° C.
3. temperatureThe solution was warmed to rt
4. stirringstirred for 1 h
5. customThe reaction mixture was then partitioned between EtOAc and sat. NH4Cl
6. dry with materialthe organic layer was dried over (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was subjected to chromatographic purification (0-10% EtOAc/hexanes gradient)