Multistep synthesis of a valsartan precursor in continuous flow

Katharina Hiebler, Sebastian Soritz, Kristian Gavric, Sam Birrer, Manuel C. Maier, Bianca Grabner, Heidrun Gruber-Woelfler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Valsartan is a potent, orally active angiotensin II receptor blocker and is widely used in the treatment of hypertension and chronic heart failure. Herein, we present an approach for the continuous synthesis of a late-stage precursor of valsartan in three steps. The applied synthetic route involves N-acylation, Suzuki-Miyaura cross-coupling and methyl ester hydrolysis. After optimization of the individual steps in batch, they were successfully transferred to continuous flow processes employing different reactor designs. The first step of the synthetic route (N-acylation) as well as the third step (methyl ester hydrolysis) are performed in coil reactor setups. The key step of the reaction cascade (Suzuki-Miyaura cross-coupling) is catalyzed by a heterogeneous palladium-substituted cerium-tin-oxide with the molecular formula Ce0.20Sn0.79Pd0.01O2-δ. The catalyst particles are implemented in an in-house developed packed-bed reactor, which features an HPLC column as fixed-bed. The combination of the individual reaction modules facilitates the consecutive performance of the three reaction steps. Using the developed multistep continuous setup, the targeted valsartan precursor was obtained with up to 96% overall yield. [Figure not available: see fulltext.].

Original languageEnglish
Number of pages12
JournalJournal of Flow Chemistry
Publication statusE-pub ahead of print - 1 Jan 2019


  • Heterogeneous catalysis
  • Multistep flow chemistry
  • Palladium
  • Valsartan

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Fluid Flow and Transfer Processes
  • Organic Chemistry


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