Reaction #69340

Reaction equation

5-hydroxy-indole

acetone 2-methoxyethyl iodide

K2CO3

2-methoxyethyl iodide

K2CO3

→

5-(2-methoxyethoxy)-1H-indole

Yield 86.2%

Solvents

toluene acetone

Conditions

Workup

1. 1
   Temperaturethe mixture is refluxed
2. 2
   OtherThe solid is removed by filtration
3. 3
   Otherthe solvent is evaporated
4. 4
   Washthe solution is washed with 2 M aqueous HCl, 10% aqueous NaHCO3, and water
5. 5
   OtherThe organic layer is dried
6. 6
   Concentrationconcentrated

Procedure

To a solution of 5-hydroxy-indole (15.2 g, 114 mmol) in 250 ml of dry acetone 2-methoxyethyl iodide (15 ml, 141 mmol, 1.25 equiv) and anhydrous K2CO3 (46.7 g, 338 mmol, 3 equiv) are added and the mixture is refluxed. Additional amounts of 0.5 equiv of 2-methoxyethyl iodide and K2CO3 are added each day. After 6 days TLC (toluene-acetone, 9:1) indicates the absence of starting material. The solid is removed by filtration, and the solvent is evaporated. The residue is taken up in dichloromethane (800 ml) and the solution is washed with 2 M aqueous HCl, 10% aqueous NaHCO3, and water. The organic layer is dried and concentrated. Column chromatography (toluene-acetone, 9:1) provides 5-(2-methoxyethoxy)-1H-indole (18.8 g, 86%). M.p. 58-60° C. (from ethyl acetate-light petroleum).

Source