6-Nitro-1H-indole → 1-(3,5-difluoro-benzyl)-6-nitro-1H-indole

HRID 1158829Notes

Reaction equation

HRID 1158829 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Br[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=1>CN(C)C=O>[F:21][C:19]1[CH:20]=[C:15]([CH:16]=[C:17]([F:22])[CH:18]=1)[CH2:14][N:10]1[C:11]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=2)[CH:8]=[CH:9]1

Participants

4

Reactant 2

HCID 785026-Nitro-1H-indoleHCID 5188963,5-Difluorobenzyl bromide

Product 1

HCID 667754591-(3,5-difluoro-benzyl)-6-nitro-1H-indoleYield 123.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

—Sodium hydride (50% dispersion in oil, 4.8 g, 100 mmol) was added to a solution of 6-nitroindole (15.0 g, 92.6 mmol) in dry dimethylformamide (750 ml). After 30 min. stirring, 1-bromomethyl-3,5-difluoro-benzene (19.5 g, 94 mmol) was added. Stirring was continued for 1 h and the reaction mixture was quenched with water. The product was extracted into ethyl acetate; the combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was stirred with heptane to produce a white solid which was collected by filtration to give 1-(3,5-difluoro-benzyl)-6-nitro-1H-indole (33 g). The product was used in the following step without further purification.

Workup

  1. stirringStirring
  2. waitwas continued for 1 h
  3. customthe reaction mixture was quenched with water
  4. extractionThe product was extracted into ethyl acetate
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. stirringThe crude product was stirred with heptane
  9. customto produce a white solid which
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-4159bac931194365819048bf141834fb
Source dataset
uspto-grants-2010_10
Patent number
US07812036B2

Reaction notes

Loading…