Afatinib is an anti-cancer drug approved for the first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). The current paper reports for the first time in Vietnam an efficient and convenient synthesis of (S)-N-(3-chloro-4-fluorophenyl)-6-nitro-7-((tetrahydrofuran-3-yl) oxy)quinazolin-4-amine (IV) as an important ether intermediate for preparing this drug. The synthesis was carried out by 2 methods: from aryl sulfone and from aryl fluoride. The process from aryl sulfon was chosen to perform at a scale of 20 g / batch with the good yield of 86.1%. This process has the advantages of mild reaction conditions, simple operation and low cost, which is useful for further optimizing and developing synthesis process of afatinib.