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Ethyl 5-methylthiophene-2-carboxylate is a useful reactant for the preparation of dithienylmaleimides via Perkin condensation, aminolysis and Suzuki coupling.

To a solution of commercially available 5-methylthiophene-2-carboxylic acid (1.0 g, 7.04 mmol) and potassium carbonate (1.94 g, 14.08 mmol) in N,N-dimethylformamide (10 mL) was added ethyl iodide (1.65 g, 10.56 mmol) dropwise. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated to give ethyl 5-methylthiophene-2-carboxylate (400 mg, 34% yield) as a light yellow oil. Electrospray ionization mass spectrometry (ESI-MS) showed m/z 171 [M + H]+, which is consistent with the calculated value C8H10O2S. The intermediate can be used directly in the subsequent reaction without further purification or characterization.

[1] European Journal of Medicinal Chemistry, 2018, vol. 150, p. 506 - 524
[2] Patent: WO2014/131855, 2014, A1. Location in patent: Page/Page column 63; 64
[3] Patent: WO2016/20307, 2016, A1. Location in patent: Page/Page column 45