Pharmacophore design to inhibit the interaction between p53 and MDM2 became a novel approach for cancer therapy. p53, known as the guardian of genome, controls the cell cycle arrest, apoptosis and DNA repair under stress. Nonetheless, when over-expressed, MDM2 causes proliferation in the cell and eventually tumorgenesis. The feedback mechanism between p53 and MDM2 arises from the interaction of p53 through the hydrophobic cleft which consists of Phe19, Trp23 and Leu26 aminoacids in the N-terminal of MDM2. In this study, it was aimed to synthesize a new, chiral 1,4-oxazepan-5-one derivatives by asymmetric synthesis. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material. Amino group was protected by trityl group then the carboxylic acid part was reduced by LiAlH4 to produce N-trityl-protected amino alcohol. Dess Martin periodinane was used for the oxidation of the alcohol to the aldehyde, then 3-chlorophenylmagnesium bromide was added to the aldehyde by Grignard reaction. Deprotection of N-trityl was performed with TFA then, coupling reactions of produced aminoalcohol with different α,β-unsaturated carboxylic acids were performed by HATU and DIPEA. Despite all of the attempts, cyclization to seven membered 1,4-oxazepan-5-one ring was never achieved.