Development of a stereoselective and scalable process for the preparation of a methylcyclobutanol-pyridyl ether

Jeffrey T Kuethe; Kallol Basu; Robert K Orr; Eric Ashley; Marc Poirier; Lushi Tan

doi:10.1016/j.bmc.2017.07.018

Development of a stereoselective and scalable process for the preparation of a methylcyclobutanol-pyridyl ether

Bioorg Med Chem. 2018 Feb 15;26(4):938-944. doi: 10.1016/j.bmc.2017.07.018. Epub 2017 Jul 11.

Authors

Jeffrey T Kuethe¹, Kallol Basu², Robert K Orr², Eric Ashley², Marc Poirier², Lushi Tan²

Affiliations

¹ Department of Process Research and Development, Merck & Co., Inc, Kenilworth, NJ 07033, USA. Electronic address: Jeffrey_Kuethe@merck.com.
² Department of Process Research and Development, Merck & Co., Inc, Kenilworth, NJ 07033, USA.

PMID: 28751197
DOI: 10.1016/j.bmc.2017.07.018

Abstract

The evolution of a scalable process for the preparation of methylcyclobutanol-pyridyl ether 1 is described. Key aspects of this development including careful control of the stereochemistry, elimination of chromatography, and application to kilogram-scale synthesis are addressed.

MeSH terms

Chromatography, Gas
Cyclobutanes / chemistry*
Drug Design
Ethers / chemical synthesis
Ethers / chemistry*
Stereoisomerism
Structure-Activity Relationship

Substances

Cyclobutanes
Ethers
cyclobutanol