During the course of a drug discovery program that culminated in the successful delivery of a clinical candidate, we sought to access (1R,2R,5R)-5-amino-2-methylcyclohexan-1-ol (I) as a moiety that could be incorporated into the lead series. Our initial synthetic efforts provided (I) as a mixture of four stereoisomers and a second generation synthesis was later developed to provide (I) as a mixture of two diastereomers. While each route was successful in delivering (I), both required the use of SFC (supercritical fluid chromatography) to achieve high stereochemical purity making both methods less attractive with increasing scale. This presentation will describe the development of an efficient SFC-free method to provide (I) with &gt; 98 % chiral purity which was significantly more cost-effective and amenable to larger scale synthesis.

Development of an efficient method to afford (1R,2R,5R)-5-amino-2-methylcyclohexan-1-ol

256th National Meeting (2018)

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