5-Nitroindole → 3-(2-Methoxy-4-methoxycarboxybenzyl)-5-nitroindole

HRID 275116Notes

Reaction equation

HRID 275116 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:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=1[O:25][CH3:26]>O1CCOCC1.[Ag-]=O>[CH3:26][O:25][C:16]1[CH:17]=[C:18]([CH:23]=[CH:24][C:15]=1[CH2:14][C:7]1[C:6]2[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[NH:9][CH:8]=1)[C:19]([O:21][CH3:22])=[O:20]

Participants

5

Reactant 2

HCID 225235-NitroindoleHCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoate

Product 1

HCID 114732633-(2-Methoxy-4-methoxycarboxybenzyl)-5-nitroindoleYield 45%

Reagents, catalysts & solvents 2

HCID 178418778HCID 178418778, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Silver (I) oxide (7.15 g.) was added to a solution of 5-nitroindole (5 g.) and methyl 4-bromomethyl-3-methoxybenzoate (B) (7.99 g.) in dioxane (30 ml.), under a nitrogen atmosphere. The mixture was stirred at 60° C. for 20 hours, dioxane removed by evaporation and ethyl acetate (50 ml.) added to the residue. The resulting suspension was separated by filtration through diatomaceous earth. The filtrate was evaporated to give a dark viscous oil, which was purified by flash chromatography on silica gel (600 ml.), eluting with 3:7 v/v ethyl acetate:hexane. The viscous yellow oil obtained was crystallized from a mixture of dichloromethane and hexane to give methyl 3-methoxy-4-(5-nitroindol-3-ylmethyl)benzoate (C) (4.6 g., 45%) as yellow needles, m.p. 153°-155° C. NMR: 3.83(s,3H, COOCH3), 3.93(s,3H, OCH3), 4.12(s,2H, CH2.Ar), 7.25(d,1H), 7.43(d,1H), 7.49(m,3H), 7.95(dd, 1H, H6 -indole), 8.47(d,1H, H4 -indole), 11.65(broad s,1H, H1 -indole).

Workup

  1. customdioxane removed by evaporation and ethyl acetate (50 ml.)
  2. additionadded to the residue
  3. customThe resulting suspension was separated by filtration through diatomaceous earth
  4. customThe filtrate was evaporated
  5. customto give a dark viscous oil, which
  6. customwas purified by flash chromatography on silica gel (600 ml.)
  7. washeluting with 3:7 v/v ethyl acetate
  8. customThe viscous yellow oil obtained
  9. customwas crystallized from a mixture of dichloromethane and hexane

Sources & evidence

ORD record
ord-29458551a96d473ca106499ecf378d29
Source dataset
uspto-grants-1995_02
Patent number
US05391758

Reaction notes

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