A convenient one-pot reaction was conducted by mixing bromoacetophenone, a functionalized α,β-unsaturated ketone and potassium hydroxide in tetrahydrofuran at room temperature, ammonium acetate was added and heated to reflux, resulting in four chemical bonds forming from easily accessible substrates. This process provides a flexible and rapid synthetic route for the construction of polysubstituted benzofuro[2,3-c]pyridines in moderate to good yields.