More Dimers - Week 3

Hi I'm Harry and I'm working in the Ballatore lab at UPenn, I'm joining in the lab's project to create a set of carboxylic acid isosteres.

After finding the dimerization issue, we tried two different things: 1. Do the same alkylation with the left-over CPD but with a 1:1:1 CPD base and benzyl bromide ratio, we did this because the dimerization might have been caused by excess CPD and not enough base and benzyl bromide to react with. 2. Do the same alkylation but this time with a methylated version of CPD. My PI predicts that the methyl group should prevent the formation of CPD dimers. The LC-MS of the product of both methods showed significantly greater yield of the product we want but unfortunately we still see the dimers. We deprotected the products and using high-performance liquid chromatography (HPLC), which accurately separates our desired product and the impurities, we collected our products.

To deal with the persisting dimerization issue, my PI suggested we change the base from KHMDS to LDA, a stronger base because he had done an akylation with LDA without encountering any dimers. To do this I had to make more protected CPD. Meanwhile we set up a separate reaction with a completely different starting material. However, the reaction did not produce any of our desired product and was considered a failed reaction.

This is the general outline of the week's lab work but also a lot of time was used in regular column chromatography, extraction, and the most annoying part: waiting for the extracted product to dry. I'm starting to repeat the same procedures for each reaction: reaction setup, monitoring using TLC and LC-MS, then quenching/extracting with water and ethyl acetate, chromatography (HPLC or regular chromatography), and finally an NMR analysis. It's great that I'm finally starting to do these steps by myself without my PI or post-doc.