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Updated: Jun 28, 2025

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Electrochemical Synthesis of a Sitagliptin Precursor
Elisabeth K Oehl1, Paul T Jirsch1, Jasmin Hammes1
1Department of Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz, Germany.
Abstract:
A novel synthesis of sitagliptin based on a redox-active ester derived from the chiral pool is reported. The key step is an electrochemical nickel-catalyzed sp2-sp3 cross-coupling reaction using inexpensive nickel foam in an undivided cell. It was successfully applied to 21 examples in up to 88% yield. These sitagliptin-analogue precursors could potentially interact with the DPP4 enzyme. A full synthesis based on our new reaction pathway provided sitagliptin in an overall yield of 33%.
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