Sodium Hydroxide → Ethyl 4-bromo-3-methylthiophene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 3-methyl-2-thiophenecarboxylate (20.0 g, 0.118 mol) and sodium hydroxide (12.3 g, 0.307 mol) in acetic acid (75 mL) was heated to 60° C. Bromine (46.9 g, 0.294 mol) was added dropwise at such a rate so as to maintain the temperature of the reaction mixture at <85 ° C. When the addition was complete, the resulting solution was stirred at 85 ° C. for 6 hours, at which time analysis by gas chromatography/mass spectrometry showed complete conversion to ethyl 4,5-dibromo-3-methyl-2-thophenecarboxylate. The solution was allowed to cool to 50 ° C. and zinc dust (15.4 g, 0.236 mol) was added in 3 gram portions such that the exotherm was controlled to remain below 85 ° C. When the addition was completed, the resulting slurry was stirred at 85° C. for one hour. The solution was filtered hot through a small bed of celite. Water (300 mL) was added and the mixture was extracted with heptanes (300 mL). The organic phase was washed with water, then concetrated to dryness to give 26.9 g (89%) as an off white oil which slowly crystallized upon standing at ambient temperature. In a similar fashion, methyl 3-methyl-2-thiophenecarboxylate may be converted methyl-4bromo-3-methyl-2-thiophenecarboxyltate in 97% yield.

Provenance & Evidence