Reaction #70658

Reaction equation

NH4Cl

n-BuLi

1,3-dihydroindol-2-one

1-(2-bromo-ethoxy)-2,4-dichlorobenzene

→

3-[2-(2,4-dichlorophenoxy)-ethyl]-1,3-dihydroindol-2-one

Solvents

THF

THF

Conditions

Workup

1. 1
   Temperaturethe reaction mixture was cooled to −70° C.
2. 2
   workup.STIRRINGThe mixture was stirred overnight at r.t
3. 3
   ExtractionThe separated aqueous layer was extracted with EtOAc three times
4. 4
   WashThe combined extracts were washed with water
5. 5
   Otherdried
6. 6
   Otherevaporated
7. 7
   OtherThe crude product was purified by silica gel chromatography first
8. 8
   Otherpurified by prep HPLC

Procedure

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).

Source