Reaction #1483079

Reaction equation

4-fluoro-benzyl bromide

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

4-fluoro-benzyl bromide

dioxane

→

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

Yield 22.0%

Solvents

ether

Conditions

Workup

1. 1
   Temperaturewere heated
2. 2
   Temperatureto reflux for 16 hr
3. 3
   Temperaturethe solution was heated
4. 4
   Temperatureat reflux an additional 4 hr
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 (0.17 g, 0.9 mmol), prepared using procedures as described in Example 1, Ag2O) (0.22 g, 0.95 mmol), 4-fluoro-benzyl bromide (0.18 g, 0.95 mmol) and dioxane (4 mL) were heated to reflux for 16 hr, then more 4-fluoro-benzyl bromide (90 mg, 0.5 mmol) was added and the solution was heated at reflux an additional 4 hr. After cooling to room temperature, the reaction mixture was diluted with ether (60 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, 1:3) to provide 3-(4-fluoro-phenylmethyl)-1-methyl-1H-indole-5-carboxylic acid methyl ester (58 mg, 22% yield).

Source