Dimethylformamide → Ethyl 5-formylthiophene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (0.588 mL, 60 mmol) in THF (20 mL) under N2 is cooled to −78° C. and treated with n-butyllithium (2.5 M in hexanes, 1.66 mL). The mixture is then warmed to 0° C. for 10 min, cooled back to −78° C., treated dropwise with a solution of thiophene-2-carboxylic acid ethyl ester (0.5 g, 3.2 mmol) in THF (12 mL), and stirred 5 min. N,N-dimethylformamide (0.324 mL, 4.16 mmol) is then added, and the reaction is allowed to warm to rt, while stirring overnight. Aqueous buffer (pH=7) is added, and the product is extracted into ethyl acetate (3×). Combined organic layers are dried, filtered, and concentrated. The resulting residue is applied to silica gel and eluted using hexanes with an ethyl acetate gradient from 0% to 40% to give 5-formyl-thiophene-2-carboxylic acid ethyl ester (325 mg).

Provenance & Evidence