Synthesis of 5-Substituted 1H-Tetrazoles from Nitriles by Continuous Flow: Application to the Synthesis of Valsartan

An efficient continuous flow process for the synthesis of 5-substituted 1H-tetrazoles is described. The process involves the reaction between a polymer-supported triorganotin azide and organic nitriles. The polymer-supported organotin azide, which is in situ generated with a polystyrene-supported triorganotin alkoxide and trimethylsilylazide, is immobilized in a packed bed reactor. This approach is simple, fast (it takes from 7.5 to 15 min), and guarantees a low concentration of tin residues in the products (<5 ppm). The process was developed to aryl-, heteroaryl-, and also alkylnitriles and was applied for the synthesis of valsartan, an angiotensin II receptor antagonist.