I. S. Young, A. Ortiz, J. Sawyer
Sep 6, 2012
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Influential Citations
5
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Journal
Organic Process Research & Development
Abstract
An efficient, scalable synthesis of (−)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (4) is described. Reduction of the pyridinium salt prepared from pyridine and benzyl chloride generated the corresponding tetrahydropyridine derivative. A two-stage epoxidation, followed by ring-opening of the epoxide with BnNH2, established the regiochemistry of the amino alcohol and served to set the trans-relationship between the amine and the hydroxyl group. The resulting racemic intermediate was then resolved by salt formation with (R)-O-acetyl mandelic acid. The process produced the O-acetyl mandelic acid salt of (−)-4 in 27% overall yield from benzyl chloride.