Improved Synthesis of Nefazodone from Phenol

A route for the synthesis of nefazodone is reported. Nefazodone was obtained with an overall yield of 37.2% from phenol. The key steps involve the improved synthesis of 5-ethyl-4-(2-phenoxyethyl)-1, 2, 4-triazol-3(2H)-one, a key intermediate in the synthesis of nefazodone. The phenol was etherified with 1, 2-dichloroethane (75%), followed by iodination-amination with Nal and CH3OH-NH3(85.7%), acylation with ethyl chloroformate (95.7%) and cyclization with propionyl hydrazine (83.6%).