Optimization and scale-up of the grandberg synthesis of 2-methyltryptamine

An efficient, safe, and cost-effective synthesis of 2-methy-ltryptamine (2), a key starting material in the synthesis of the histone deacetylase inhibitor LBH589 (1) is described. The reaction of pheny1hydrazine (7) with a stoichiometric amount of 5-chloro-2-pentanone (8) in aqueous ethanol at reflux furnished crude 2-methyltryptamine (2). The product 2 was obtained in 47% yield and > 99% purity after crystallization from toluene.