A synthesis of 2-amino-4-(R)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile derivatives (4a-l) in single flasks containing aromatic aldehydes (1a-l), malononitrile (2), and dimedone (3) by using green catalyst, extract of orange without solvent under ultrasound irradiations and reflux condition. Synthesis of 2-amino-4-(R)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile derivatives (4a-l) show potent in-vitro anti-inflammatory activity. All synthesized compounds were characterized by FTIR, ¹H NMR, ¹³C NMR and mass spectroscopic data & elemental analysis.