Scale up of 6-methylene-1,4-oxazepane and 6-oxo-1,4-oxazepane derivatives as key intermediates for MedChem relevant building blocks synthesis | Poster Board #3427

As part of our program to expand MedChem relevant building block chemical space the scale up (up to 300 g from 1 run) of Boc-protected 6-methylene-1,4-oxazepane and 6-oxo-1,4-oxazepane was accomplished. The reaction sequence was based on the [3+4] cyclization of Boc-protected aminoethanol and 3-chloro-2-(chloromethyl)prop-1-ene with followed Ru-catalyzed oxidation of exo methylene group. The applying to the parent or modified protocol the methyl substituted ,4-oxazepane was accomplished. The [3+4] cyclization of Boc-protected aminoethanols gives unexpected results: the scale up of mono-methyl substituted derivatives failed while gem-dimethyl substituted substrates were scaled up successfully. The results are the next proving of the Thorpe–Ingold effect. The successful scale up project allow us to elaborate the cost effective way to the set of the valuable for MedChem functionalized oxo-1,4-oxazepanes via well-known functional group interconversion.