TCMDC-123812 and 123794, pending purification.

09 Oct
Published by pylioja


Request for Help

I'm now fairly confident that I've made TCMDC-123794 and TCMDC-123812. By fairly confident I mean that I've got a reasonable looking but crude 1H NMR and low res. mass spec of both of the compounds. They are not clean by NMR after a column and the yield of the reaction was pretty bad (~20%). Still this isn't too bad for a first go, using a quick and dirty acid chloride. Most of the mass seems to go toward turning the acid into the anhydride. This is supported by NMR but mass spec hasn't given a positive result so far. The side-chain for TCMDC-123794 wasn't clean to begin when I originally tried this but I have some cleaner material after a column so that shouldn't cause any problems in the future. Using DIC/DMAP for the same transformation (PMY 10-3 and 11-3) gave the same products but contaminated with the urea by-product after chromatography. Again, most of the mass goes toward what appears to be the anhydride. This anhydride seems to be very stable. Even after 15 hours at 60 °C, this does not convert into the desired product. Nevertheless, with a bit of purification we've got these two analogues sorted. If anyone wants some for testing, then get in touch.
It looks like the NaCl2 oxidations were giving the acid to some degree. The material produced by that method (e.g PMY 3-8) contained an impurity visible in the carbon NMR spectra. This would explain the dubious integral in the proton NMR that made me doubt the product in the first place. I haven't spent any more time on the oxidation for the moment as I can produce the acid simply from the ester. If anyone does try it out, it would be useful to get the results. It does work, but something seems to be going wrong along the way.
Thanks to everyone who have commented and answered to posts in various places (keep it up!). I've had a good few comments on facebook, a couple of emails and another few comments on here. I'm hoping more people start posting here as it makes centralised discussion easier.