Synthesis of Bicyclic Ortho Esters by Epoxy Ester Rearrangements and Study of Their Ring-Opening Reactions

In my hands, using 37 % formalin and water as solvent as reported did not produce a yield comparable to that in the paper (~5 % vs. 60 % reported). Instead, using 1.07 eq. paraformaldehyde in ethanol as reported by D'hooghe worked well (DOI: Synthesis of Potent and Selective HDAC6 Inhibitors Bearing a Cyclohexane‐ or Cycloheptane‐Annulated 1,5‐Benzothiazepine Scaffold) as they reported. The product seems potentially volatile in my hands, so my lower yield could be due to loss of product on vacuum. Would consider running the column in lower boiling point solvents.