Given the large quantities of drug substance that could be required, cost-effective syntheses are needed. A key feature of pretomanid is the dihydro-1,3-oxazine, containing an oxygen-substituted asymmetric center on the C3 unit (Figure ). One could foresee installation of this fragment from an (S)-glycidol derivative, and not surprisingly many of the current pretomanid routes make use of functionalized glycidols. Glycidyl pivalate appears to be a particularly important variant. 3 Enantiomers of optically active glycidol are of considerable expense, however, construction from less expensive precursors would be desirable. Epichlorohydrin is a feedstock chemical, and its pure enantiomers are highly available in comparison to those of glycidol. As a result, (R)-epichlorohydrin is approximately 5-6% of the cost 4 of (S)-glycidol and could thus form the basis for a more costeffective route to this intermediate. Numerous reports describe reaction of epichlorohydrin with carboxylates, particularly hindered carboxylates, as the ensuing glycidyl esters are used in alkyd resins, paints, coatings, and acrylate monomer compositions. Fewer reports detail the reaction of enantiopure epichlorohydrin with carboxylic acid derivatives. This work describes development of a practical route to (S)-glycidyl pivalate from low-cost and readily available (R)-epichlorohydrin and pivalic acid.