Synthesis of an H3 Antagonist via Sequential One-Pot Additions of a Magnesium Ate Complex and an Amine to a 1,4-Ketoester followed by Carbonyl-Directed Fluoride Addition
- Joel M. Hawkins
- Pascal Dubé
- Mark T. Maloney
- Lulin Wei. Marcus Ewing
- Stephen M. Chesnut
- Joshua R. Denette
- Brett M. Lillie
- Rajappa Vaidyanathan
- Pharmaceutical Sciences, Pfizer Inc., Groton, USARead the publication that featured this abstract
We describe the development of an efficient and scalable process for the preparation of fluorocyclobutane-containing H3 antagonist, 1. The synthesis was accomplished by the chemoselective addition of a magnesium ate complex and an amine to a 1,4-ketoester in a one-pot sequence, followed by a diastereoselective carbonyl-directed fluorination. The chemoselective addition of the magnesium ate complex to the ketoester benefited from tight stoichiometric control, short addition times, and lower reaction temperatures, and thus was amenable to rapid mixing and excellent heat transfer in a flow reactor.
The Vapourtec R-Series is, quite simply, unrivalled for flow chemistry
- Flexible |
- Precise |
The R-Series is undoubtedly the most versatile, modular flow chemistry system available today.
The Vapourtec E-Series is the perfect introductory system for flow chemistry
- Robust |
- Easy to use |
The E-Series is a robust and affordable, entry level flow chemistry system designed for reliability and ease of use.