4-Bromo-5-methyl-2-thiophenecarboxylic acid

Synthesis

29421-73-6

29421-99-6

a) 27.65 g (108 mmol) of 2-methyl-3,5-dibromothiophene (prepared according to the method of Kano, S. et al, Heterocycles 20(10):2035, 1983) was dissolved in 280 mL of anhydrous tetrahydrofuran and cooled to -78°C. To this solution was added, over a 10-minute period, 54 mL (108 mmol) of a 2 M n-butyllithium in cyclohexane solution. After stirring at -78°C for 20 min, dry carbon dioxide gas was passed into the reaction system for 1.5 hr while the mixture was allowed to warm slowly to room temperature. Upon completion of the reaction, 100 mL of 6N hydrochloric acid was carefully added. The organic and aqueous layers were separated and the aqueous layer was extracted with ether (4 x 50 mL). All organic layers were combined, washed with brine and dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure to give 22.4 g (94% yield) of 4-bromo-5-methylthiophene-2-carboxylic acid as an off-white solid.1H-NMR (DMSO-d6; 300 MHz) δ 13.34 (br s, 1H), 7.61 (s, 1H), 2.41 (s, 3H).

References