A Convergent Continuous Multistep Process for the Preparation of C<inf>4</inf>-Oxime-Substituted Thiazoles

Abstract

We report a strategy designed for the rapid and convergent assembly of C4-oxime substituted thiazoles. Our approach relied on 3-bromo-2-oxopropanal O-methyl oxime 7 as a key building block. A three-step sequence to 7 was designed, which for safety concerns, could only be operated in batch mode on limited scales (<< 100g). We describe herein how we addressed such a limitation, by designing a multistep continuous synthesis of this intermediate and further demonstrate the advantages of flow reactor configuration upon scaling up.