|Credit: Hong et al., Org. Process. Res. Dev.|
This group from Roche Palo Alto, in the midst of a synthesis of an isoquinolinone, used them to test their chemistry:
On a 20-g scale, the aminolysis reaction was conducted at 130 °C in a stirred Hastelloy C autoclave using 4−5 equiv of dimethylamine. At pressures ranging from 120 to 160 psig, the reaction was complete within 16 h. However, the fact that 1 equiv of fluoride will be released during the aminolysis could lead to etching of the glass-lined autoclave under the rather vigorous conditions employed. The etching test with glass coupons confirmed this possibility as the glass surfaces of the samples were seriously degraded. This observation of significant glass erosion prompted an investigation of alternate means to effect this transformation that would be more compatible with existing equipment...
...Another approach to render the aminolysis of 3 (CJ's note: the starting material) compatibleThe use of TMSOEt to absorb the released fluoride ion is a good idea -- I'll have to remember it. Also, it's obvious that you'd have glass coupons (as opposed to the 316 stainless or Hastelloy ones that I've seen/heard of), but I hadn't heard of them until now. (How do you not break the glass coupons? Do they just rest on the bottom of the reactor?)
with the glass-lined autoclave would be to scavenge the fluoride ions generated from the reaction mixture as they form. To this end, several experiments incorporating TMSOEt as a component of the reaction mixture were performed in Parr Hastelloy pressure vessels containing samples of the DeDietrich glass liner. On a 10−50-g scale, addition of 1.5−3.0 equiv of the silane to the standard aminolysis mixture had no adverse effect on the course of the substitution reaction other than a modest reduction in apparent reaction rate. However, the glass liner samples were recovered essentially intact, even upon prolonged heating at 145 °C. Complete conversion of 3 was observed within 24−36 h.
1. Hong, J.-B.; Davidson, J.P.; Jin, Q.; Lee, G.R.; Matchett, M.; O’Brien, E.; Welch, M.; Bingenheimer, B.; Sarma, K. "Development of a Scalable Synthesis of a Bruton’s Tyrosine Kinase Inhibitor via C–N and C–C Bond Couplings as an End Game Strategy." Org. Process Res. Dev., ASAP. DOI: 10.1021/op4001077