Ethanol → Ethyl 4-bromo-1H-indole-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl bromoacetate (42 g) in ethanol (120 mL) was added a solution of NaN3 (25 g) in water (60 ml). The mixture was stirred at reflux for 4 hours. The mixture was concentrated under vacuum and the residue was partitioned between ether (300 mL) and water (200 mL). The aqueous layer was further extracted with ether. The combined extracts were washed with water (×3), brine and dried over Na2SO4. After filtration, careful concentration of solvent gave ethyl azidoacetate (26 g) which was dissolved in ethanol (100 ml) and 2-bromobenzaldehyde (12.5 g) was added to the solution which was then added dropwise to a cooled (−15° C.) solution of sodium ethoxide (prepared from Na (5.2 g) and ethanol (60 ml)). The mixture was stirred at 0° C. for 4 hours before poured into a mixture of ice and saturated aqueous NH4Cl solution. The mixture was filtered and the precipitate was washed with water and dissolved in ethyl acetate and dried over Na2SO4. Concentration of solvent gave crude intermediate, which was dissolved in xylene (100 ml) and added dropwise to refluxing xylene under nitrogen. After the addition, the mixture was stirred at reflux overnight. Concentration of the mixture under vacuum gave the crude product, which was purified by silica gel chromatography (2% ethyl acetate in hexane).

Provenance & Evidence