First reported scale-up of a ring closing metathesis (RCM) reaction

13 October 2005

The advent of catalysts which effect RCM under synthetically useful conditions has dramatically changed the way researchers approach total synthesis. Now the first large scale use of RCM has been published by workers from Boehringer Ingleheim.

The reaction was carried out on a 3000-litre scale using a ruthenium-based first generation Hoveyda catalyst in toluene to allow higher  temperatures for a shorter reaction time. The reaction was run at 118ml of toluene per g of substrate and an 83% assay yield of 90% pure
product was obtained. Almost 400kg of the intermediate shown have been prepared by this reaction.

T. Nicola et al, Org. Proc. Res. Dev., 2005, 9, 513-515.