An environmentally friendly catalyst-free synthesis protocol for functionalized 1,4-dihydropyridine derivatives involving four components under ultrasonic irradiation in aqueous ethanol is reported. Eleven new compounds are synthesized using multi-component one-pot reaction between dimethylacetylenedicarboxylate, 2-fluoroaniline, malononitrile and various substituted aldehydes. The establishment of multiple carbon–carbon bonds occurs in the absence of any hazardous organic solvents or catalysts. The target compounds were obtained in excellent yields (89–96%). All the new compounds were identified and validated by IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, ¹⁵N NMR and HRMS spectral data. The new procedure has noteworthy advantages including safety, short reaction times, environmentally benign mild conditions and high yields.