Benzyl Bromide → 1-benzyl-1H-indole-3-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a solution of 1H-indole-3-carbaldehyde (25.0g, 172 mmol) in tetrahydrofuran (500 mL) cooled to 0° C. with an ice-bath and under an inert atmosphere was slowly added sodium hydride (4.96 g, 207 mmol), such that the temperature of the mixture remained less that 5° C. After complete addition, the mixture was allowed to stir at 0° C. for 15 minutes. To the mixture was added benzyl bromide (35.4 g, 207 mmol). The ice bath was removed and the mixture was allowed to warm to room temperature over 1.5 hours. The mixture was then partitioned between brine and ethyl acetate. The layers were separated and the aqueous layer was extracted with two additional portions of ethyl acetate. The combined organics were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting red solids were dissolved in methylene chloride and the solution was filtered through a plug of silica gel. The filtrate was concentrated under reduced pressure until a precipitate began to form. The product was crystallized out of the solution by the addition of an eight-fold volume of hexane. The red-tinted solid was isolated by vacuum filtration, and the process was repeated one additional time to give 1-benzyl-1H-indole-3-carbaldehyde (38.8 g, 96%) as an off-white powder. 1H NMR (400 MHz, CDCl3); δ 9.98 (s, 1H), 8.32 (m, 1H), 7.71 (s, 1H), 7.34 (m, 6H), 7.18 (m, 2H), 5.36 (s, 2H).

Provenance & Evidence