A Convergent Continuous Multistep Process for the Preparation of C4-Oxime-Substituted Thiazoles

2018 
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 (≪100 g). 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.
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