Sulfur Dioxide → N-[[3-(1,3-dioxolan-2-yl)-2-thienyl]sulfonyl]glycine ethyl ester

Participants

Reaction Steps

To a solution of thiophene-3-carboxaldehyde ethylene acetal (13.27 g, 85.1 mmol) in anhydrous THF (200 mL) at -70° C. was added n-butyllithium (2.5M, 37.4 mL, 93.6 mmol). The solution was stirred for 50 min; a white precipitate formed. Sulfur dioxide was passed through the solution for about 5 min and the mixture was warmed to ambient temperature. The volatiles were evaporated and the residue suspended in methylene chloride (200 mL); this mixture was cooled (0° C.) and N-chlorosuccinimide (14.77 g, 110.6 mmol) added. After stirring at ambient temperature for 3 h the mixture was filtered. The filter pad was washed with ethyl acetate (300 mL) and the combined filtrates were cooled (ice bath) and mixed with a saturated aqueous solution of sodium bicarbonate (250 mL) and glycine ethyl ester hydrochloride (33.99 g, 221 mmol). The mixture was stirred at ambient temperature for 16 h and the organic layer was separated, dried (MgSO4), and evaporated to a residue which was purified by column chromatography (silica, 40% ethyl acetate in hexane) to give a colorless liquid (16.55 g, 61%).

Provenance & Evidence