盐酸埃罗替尼中间体3,4-二(2-甲氧基乙氧基)苯腈合成新工艺研究

New Synthetic Process of 3,4-Bis(2-methoxyethoxy)benzonitrile as an Intermediate of Erlotinib Hydrochloride

盐酸埃罗替尼是第一个应用于临床的口服表皮生长因子受体(EGFR)抑制剂,其中3,4-二(2-甲氧基乙氧基)苯腈是盐酸埃罗替尼合成的关键中间体。以儿茶酚为原料,经醚化、Vilsmeier反应、氰基化3步反应合成了3,4-二(2-甲氧基乙氧基)苯腈,总收率达61.2%,产品结构经NMR和MS确证。该工艺原料价廉易得、操作简便、成本较低、收率较高,适合工业化生产。

Erlotinib hydrochloride is the first oral epidermal growth factor receptor(EGFR) inhibitor used in clinic.Therein,3,4-bis(2-methoxyethoxy)benzonitrile is a key intermediate for the synthesis of Erlotinib hydrochloride.Using catechol as a raw material,we synthesized 3,4-bis(2-methoxyethoxy)benzonitrile with overall yield of 61.2% through etherification,Vilsmeier reaction,and cyanation.Moreover,the structure of the target compound is confirmed by NMR and MS.The process is suitable for industrial production owing toits advantages of available raw materials,simple operation,lower cost,and high yield.