My student would like to make di-tert-butylhydroxymethylphosphonate, (t-butylO)2P(O)-CH2OH. He found a procedure in the patent literature that suggested using microwaving for 20 minutes (90 °C) in the presence of 0.1 equivalents of triethylamine and an excess of para-formaldehyde. Based on previous experience (mentioned upthread) I am a little bit worried about loss of the tert-butyl protecting groups, but I told him to go ahead on a small scale. If it fails, we have previously used a route involving Michaelis-Becker chemistry. It is unclear to me how the temperature is known in this procedure, inasmuch as it is done in a sealed vial. Although others in our department do, we don't have any experience with microwave reactions, so any suggestions would be appreciated.
Synthesis of high relaxivity chelates for potential use as MRI contrast agents
Caravan, Peter D.; Jacques, Vincent; Dumas, Stephane; Sun, Wei-Chuan; Zhou, Kevin L.; Schmitt-Willich, Heribert
Assignee Epix Pharmaceuticals, Inc., USA