biostudies-literatureHinton HNational Science Foundation5087https://www.ebi.ac.uk/biostudies/studies/S-EPMC10343380biostudies-literatureUnknown28(13)This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.).Molecules (Basel, Switzerland)Scalable Preparation of the Masked Acyl Cyanide TBS-MAC.PMC103433801848257Hinton HPatterson JPigza JHume JPatel KfalseScalable Preparation of the Masked Acyl Cyanide TBS-MAC.This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.).2023-01-01T00:00:00Z2023 Jun2025-04-19T04:59:53.484Z2025-04-19T04:59:53.484ZS-EPMC103433803744674910.3390/molecules28135087