To a mixture of ethyl 3-(4-(4-aminophenyl)-3-(4-cyano-2-methylphenyl)thiophen-2-yl)propanoate (180 mg, 0.46 mmol) in a mixture solvent of HBr (48%, 3 mL) and water (1 mL) was added dropwise a solution of NaNO2 (32 mg, 0.46 mmol) in water (0.5 mL). Then the mixture was stirred at 0° C. for 1 hour. Then CuBr (66 mg, 0.46 mmol) was added and the mixture was stirred at 0° C. for additional 1 hour. The reaction mixture was extracted with EtOAc and the combined organic layer was dried over Na2SO4, concentrated in vacuo to give crude ethyl 3-(4-(4-bromophenyl)-3-(4-cyano-2-methylphenyl)thiophen-2-yl)propanoate, which was used in the next step directly.
