Abstract: OBJECTIVE To improve the synthetic method of ambrisentan. METHODS As the starting material, methyl 2-hydroxy-3-methoxy-3,3-diphenylpropionate was firstly hydrolyzed and then resoluted with (R)-(+)-1-phenylethylamine to give (S)-2-hydroxyl-3-methoxy-3,3-diphenylpropionic acid, and finally reacted with 4,6-dimethyl-2-methylsulfonyl pyrimidine in the presence of LiNH₂ to obtain ambrisentan. RESULTS The product was detected by HPLC with the purity of 99.91% and the enantiomeric excess of 99.9%, and the overall yield was 33.8%. The structure of the product had been confirmed by ¹H-NMR, ¹³C-NMR and ESI-MS. CONCLUSION This synthetic method is easy to operate with reliable quality and low cost, and it is suitable for industrial production.