反应详情

温度

0 °C

To a suspension of 1,3-dihydroindol-2-one (13.3 g, 0.10 mol) in THF (350 mL) was added dropwise n-BuLi (2.5 M in hexane, 84.0 mL, 0.21 mol) at 0° C. under nitrogen atmosphere. After stirring for 1 h at 0° C., the reaction mixture was cooled to −70° C. and a solution of 1-(2-bromo-ethoxy)-2,4-dichlorobenzene (32.4 g, 0.12 mmol) in THF (100 mL) was added dropwise. The mixture was stirred overnight at r.t and poured into NH4Cl (aq. sat.). The separated aqueous layer was extracted with EtOAc three times. The combined extracts were washed with water, dried and evaporated. The crude product was purified by silica gel chromatography first and then purified by prep HPLC to give 3-[2-(2,4-dichlorophenoxy)-ethyl]-1,3-dihydroindol-2-one (1.9 g, 5.8% yield) as an off-white solid. 1H NMR (DMSO-d6) δ: 10.38 (s, 1H), 7.54 (d, 1H, J=2.4 Hz), 7.35 (dd, 1H, J1=8.8 Hz, J2=2.4 Hz), 7.28 (1H, J=7.2 Hz), 7.17-7.13 (m, 2H), 6.92 (t, 1H, J=7.2 Hz), 6.81 (d, 1H, J=7.6 Hz), 4.24-4.20 (m, 2H), 3.59 (t, 1H, J=6.8 Hz), 2.29-2.19 (m, 2H).

1. temperaturethe reaction mixture was cooled to −70° C.
2. stirringThe mixture was stirred overnight at r.t
3. extractionThe separated aqueous layer was extracted with EtOAc three times
4. washThe combined extracts were washed with water
5. customdried
6. customevaporated
7. customThe crude product was purified by silica gel chromatography first
8. custompurified by prep HPLC