5-Nitroindole → 3-(4-Cyano-2-methoxybenzyl)-5-nitroindole

HRID 1080792Notes

Reaction equation

HRID 1080792 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].Br[CH2:14][C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[O:23][CH3:24]>O1CCOCC1.[Ag-]=O.[Ag]=O>[C:19]([C:18]1[CH:21]=[CH:22][C:15]([CH2:14][C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=2)=[C:16]([O:23][CH3:24])[CH:17]=1)#[N:20]

Participants

6

Reactant 2

HCID 225235-NitroindoleHCID 147529954-(Bromomethyl)-3-methoxybenzonitrile

Product 1

HCID 233659183-(4-Cyano-2-methoxybenzyl)-5-nitroindoleYield 30.5%

Reagents, catalysts & solvents 3

HCID 92152Silver(II) oxideCatalystHCID 178418778HCID 178418778, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

An efficiently stirred mixture of 5-nitroindole (3.24 g.), bromide (W) (4.57 g.) and silver (I) oxide (4.87 g.) in dry dioxane (90 ml.) was heated at 100° C. for 5 hours. Additional silver oxide (2 g.) was added, and heating continued for 1 hour. The cooled mixture was evaporated, the residue diluted with dichloromethane, filtered, washing the filter cake with dichloromethane until the washings were colorless, and the combined filtrate evaporated. The product was purified by flash chromatography on silica gel, eluting with 3:7 v/v ethyl acetate:hexane, giving a product which was crystallized from a mixture of ethyl acetate and hexane to give 3-(4-cyano-2-methoxybenzyl)-5-nitroindole (1.87 g., 30%) as a yellow powder, m.p. 204°-206° C.; partial NMR (80 MHz, DMSO-d6): 3.92(s,3H, OMe); 4.12(s,2H, ArCH2).

Workup

  1. temperatureheating
  2. customThe cooled mixture was evaporated
  3. additionthe residue diluted with dichloromethane
  4. filtrationfiltered
  5. washwashing the filter cake with dichloromethane until the washings
  6. customthe combined filtrate evaporated
  7. customThe product was purified by flash chromatography on silica gel
  8. washeluting with 3:7 v/v ethyl acetate
  9. customhexane, giving a product which
  10. customwas crystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-348eaf9f28c74f33a8c5d1959dc5d433
Source dataset
uspto-grants-1996_12
Patent number
US05583152

Reaction notes

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