Imidazole → HCID 18973329, compound

Participants

Reaction Steps

There were dissolved, in 40 ml of dimethylformamide, 5.14 g of 1-(2-hydroxy-2-phenylethyl)indole-4-carboxylate prepared in Example 320, 2.37 g of imidazole and 4.50 g of t-butyldimethylsilyl chloride and the resulting solution was stirred at room temperature for 21 hours. The solution was then poured into 100 ml of water and extracted with ethyl acetate (100 ml×2). The extract was washed in order with a 10% citric acid aqueous solution, a saturated sodium hydrogen carbonate aqueous solution and a saturated common salt solution, then dried over anhydrous sodium sulfate and the solvent was removed by evaporation under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to give 6.97 g of a pale yellow oily substance. The substance was dissolved in 20 ml of tetrahydrofuran and then dropwise added to a suspension of lithium aluminum hydride (516 mg) in tetrahydrofuran (40 ml) with ice-cooling. After stirring at room temperature for 1.5 hour, 0.52 ml of water, 0.52 ml of a 15% aqueous sodium hydroxide solution and 1.56 ml of water were, in order, added to the mixture, followed by drying over potassium carbonate, filtration and removal of the solvent through evaporation under reduced pressure to give 6.42 g of a colorless oily substance. This substance was dissolved in 70 ml of methylene chloride, followed by addition of 37.5 g of manganese dioxide, stirring at room temperature for 17 hours, filtration through a Celite layer, removal of the solvent through evaporation under reduced pressure to give 5.1 g of a pale yellow oily substance. The substance was dissolved in 40 ml of tetrahydrofuran, followed by addition of 25.8 ml of a 1.0M tetrabutylammonium fluoride solution and stirring at room temperature for 3.5 hours. water (50 ml) was added to the solution, extracted with ethyl acetate (100 ml×2), followed by washing of the extract with, in order, 5% hydrochloric acid, a saturated sodium hydrogen carbonate aqueous solution and a saturated common salt solution, drying over anhydrous sodium sulfate and removal of the solvent through evaporation under reduced pressure to give a crude product. The crude product was purified by silica gel column chromatography to give 3.55 g of 1-(2-hydroxy-2-phenylethyl)indole-4-carbaldehyde as a yellow oily substance. The yield thereof was found to be 75%.

Provenance & Evidence