Process chemistry: Difference between revisions

Analysis of the cross-methathesis reaction revealed that the conformation of the acyclic precursor had a profound impact on the formation of dimers and oligomers in the reaction mixture. By installing a [[Tert-butyloxycarbonyl protecting group|Boc protecting group]] at the C-4 amide nitrogen, the Boehringer Ingelheim chemists were able to shift the site of initiation from the vinylcyclopropane moiety to the nonenoic acid moiety, improving the rate of the intramolecular reaction and decreasing the risk of epimerization. Additionally, the catalyst employed was switched from the expensive 1st generation Hoveyda catalyst to the more reactive, less expensive Grela catalyst.<ref>{{cite journal|last=Grela|first=K.|author2=Harutyunyan, S. |author3=Michrowska, A. |title=A highly efficient ruthenium catalyst for metathesis reactions|journal=Angew. Chem. Int. Ed.|year=2002|volume=41|pages=4038–4040|doi=10.1002/1521-3773(20021104)41:21<4038::aid-anie4038>3.0.co;2-0|url=https://pure.rug.nl/ws/files/3040319/2002AngewChemIntEdGrela.pdf}}</ref> These modifications allowed the process chemists to run the reaction at a standard reaction dilution of 0.1-0.2 M, given that the rates of competing dimerization and oligomerization reactions was so dramatically reduced.