Selection and Scale-Up Evaluation of an Alternative Route to (−)-(3R,4R)‑1-Benzyl-4-(benzylamino)piperidin-3-ol

Selection and Scale-Up Evaluation of an Alternative Route to (−)-(3R,4R)‑1-Benzyl-4-(benzylamino)piperidin-3-ol

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 epo...

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Bibliographic Details
Published in:Organic process research & development Vol. 16; no. 9; pp. 1558 - 1565
Main Authors: Young, Ian S, Ortiz, Adrian, Sawyer, James R, Conlon, David A, Buono, Frederic G, Leung, Simon W, Burt, Justin L, Sortore, Eric W
Format: Journal Article
Language:English
Published: American Chemical Society 21-09-2012
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/op300174w