A total synthesis of brevisamide, a marine monocyclic ether amide isolated from the dinoflagellate Karenia brevis, has been achieved in 18 steps starting from 4-(benzyloxy)butanol. The synthesis involves oxiranyl anion coupling between an epoxy sulfone and a triflate, intramolecular etherification of a hydroxy-bromoketone, diastereoselective introduction of the axial methyl group by hydroxyl-directed hydrogenation of an exocyclic olefin, and installation of an acetamide side chain by nucleophilic substitution of an N-acetyl carbamate. The dienal side chain is assembled using a Horner-Wadsworth-Emmons reaction to complete the synthesis.

Benzyl acetylcarbamate potassium salt (BENAC-K) has been developed as a simple nucleophilic acetamide equivalent. A broad variety of alkyl halides were converted into benzyloxycarbonyl-protected N-alkylacetamides in high yields by simple treatment with an almost equimolar (1.1 equiv) amount of BENAC-K in a polar solvent.