Cascade 3 – a) synthesis of Valsartan

Valsartan is synthesized continuously in a fixed bed reactor with three different segments. The first step is catalyzed by a base, e.g. K2CO3, which is also needed for the Suzuki-Miyaura coupling and thus can be used for both reactions. For the latter self-made heteroge¬neous Pd-catalysts will be used. These catalysts are either Ce-Sn-Pd (CexSn1-xPd0.01O2-δ) catalysts or Pd-immobilized via a bis(oxazoline) ligand on functionalized silica-gel particles or monoliths. Preliminary experiments will show if it is necessary to protect the tetrazole ring at the free amine position. The last step of the synthesis involves the conversion of the methylester to the acid using an immobilized hydrolase.