Reaction #1483074

Reaction equation

dioxane

1-methyl-1H-indole-5-carboxylic acid methyl ester

4-nitro-benzyl bromide

4-nitro-benzyl bromide

→

1-methyl-3-(4-nitro-phenylmethyl)-1H-indole-5-carboxylic acid methyl ester

Yield 58.6%

Solvents

ether

ethyl acetate

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureto reflux for 25 hr
3. 3
   Temperaturethe solution was heated
4. 4
   Temperatureat reflux an additional 4 days
5. 5
   Washwashed with aq. NH4Cl (50 mL)
6. 6
   DryingThe organic layer was dried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated

Procedure

A solution of 1-methyl-1H-indole-5-carboxylic acid methyl ester (0.38 g, 2.0 mmol), prepared using procedures as described in Example 1, Ag2O (0.51 g, 2.2 mmol), 4-nitro-benzyl bromide (0.48 g, 2.2 mmol) and dioxane (6 mL) was heated to reflux for 25 hr, then more 4-nitro-benzyl bromide (0.48 g, 2.2 mmol) was added and the solution was heated at reflux an additional 4 days. After cooling to room temperature, the reaction mixture was diluted with ether (50 mL) and ethyl acetate (50 mL), washed with aq. NH4Cl (50 mL) and then brine (50 mL). The organic layer was dried over MgSO4, filtered and concentrated. The remaining residue was subjected to flash chromatography (ethyl acetate/hexane, 1:4) to provide of 1-methyl-3-(4-nitro-phenylmethyl)-1H-indole-5-carboxylic acid methyl ester (0.38 g, 58% yield). 1H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H), 8.16 (d, 2H, J=8.3 Hz), 7.98 (d, 1H, J=8.3 Hz), 7.45 (d, 2H, J=8.3 Hz), 7.35 (d, 1H, J=8.3 Hz), 6.90 (s, 1H), 4.25 (s, 2H), 3.94 (s, 3H), 3.82 (s, 3H).

Source