Dimethylformamide → 2-Hydroxymethyl-3-thiophenecarboxaldehyde

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Reaction Steps

To a stirred, chilled, (-70° C.) solution of 3-bromo-2-hydroxymethylthiophene (19.0 g) and tetrahydrofuran (250 ml) was added n-butyllithium (88 ml of a 2.5M solution in hexanes), under nitrogen, over 45 mins. The solution was stirred and chilled for 1 hr and was transferred via canula to a vessel containing a solution of N,N-dimethylformamide (7.9 g) and tetrahydrofuran (250 ml). The mixture was allowed to warm to ambient temperature overnight, with stirring. Methanol (20 ml) and water (200 ml) were added. The organic phase was removed in vacuo, and the residue was extracted with dichloromethane. The combined organic phase was washed with 5% sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by high performance liquid chromatography (silica gel, eluted with 40% ethyl acetate in hexane). The appropriate fractions were combined and evaporated to afford 3.5 g (35%) of 2-hydroxymethyl-3-thiophenecarboxaldehyde.

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