I draw ever closer to something that resembles my target molecule. Today’s attempt at chemistry comes in the form of adding a TBDPS group to a primary alcohol I spent yesterday making. The reaction in question was put on last night and worked up this morning. TBDPSCl, imidazole, and my substrate at room temperature in DMF was stirred overnight and quenched and worked up in the normal way this morning.
The literature reference for this compound told me it required purification by column chromatography (a phrase that always makes my blood run cold) eluting with 2:1 petrol and ethyl acetate. This compound has taken me a few days to prepare and I learnt very quickly as a PhD student not to trust the literature on stuff like this so I thought I would play it safe and use 4:1 instead, just to increase the separation of the three spots. “This should be a nice easy column, I’ll be done in an hour or so” I thought to myself and set about taking fractions. The first two spots came off within the first ten fractions along with the first signs of the major product which I can only assume to be the one I want. NMR of the first two fractions showed me that one was assorted crap and one was what I assume to be unreacted TBDPSCl. I then increased the amount of ethyl acetate in my solvent mixture and continued collecting fraction after fraction after fraction...
Eighty fractions later following a particularly interesting regimen of “take fraction, TLC, stain, cry, repeat” my patience was starting to wane somewhat as this final product showed absolutely no signs of slowing down. As I’m sure I have mentioned previously, I will do almost anything to avoid running a column but this one really takes the cake. I assume what is coming off is pure (I’m removing the solvent as I write this) but cannot describe to the non-chemists amongst those of you who read this how boring it is collecting fractions that come out the bottom of a column. I don’t make anything which is a nice colour, I don’t make anything fluorescent and I don’t make anything which smells nice so I just have to sit there and hope my column is working OK before I check at the end. This purgatory can and does go on for extended periods of time and takes up a solid proportion of my time in the lab. Anyway, if this stuff is not completely pure and in at least 95% yield I’m going to be dramatically unimpressed (I joke of course, anything remotely positive will do for me at the moment).
Anyway, I have training tonight so I’m going to spend the next two hours running around in the cold to hopefully let off some steam so I can get back “in the game” so to speak in the morning. Tonight I can only pray to the chromatography gods in the hope that tomorrow will provide me with a slightly more fruitful way to spend my time, like doing some chemistry that might actually be publishable at some point in the future.