Ammonium Chloride → 3-[2-(2,4-Dichlorophenoxy)-ethyl]-1,3-dihydroindol-2-one

HRID 42380Notes

Reaction equation

HRID 42380 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[Li]CCCC.Br[CH2:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[Cl:27].[NH4+].[Cl-]>C1COCC1>[Cl:27][C:21]1[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:20]=1[O:19][CH2:18][CH2:17][CH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][C:2]1=[O:10]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 1388811-(2-Bromoethoxy)-2,4-dichlorobenzeneHCID 321710OxindoleHCID 178418339Butyllithium

Product 1

HCID 593474303-[2-(2,4-Dichlorophenoxy)-ethyl]-1,3-dihydroindol-2-oneYield 4,914.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

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).

Workup

  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

Sources & evidence

ORD record
ord-abe176a1d0464b77853dd1b479676d07
Source dataset
uspto-grants-2013_09
Patent number
US08536195B2

Reaction notes

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