1384733-04-3

Upstream product

• 110-86-1 pyridine 
• 100-44-7 benzyl chloride 
• 725715-12-8 3-(phenylmethyl)-7-oxa-3-azabicyclo[4.1.0]heptane 
• 40240-12-8 1-benzyl-1,2,3,6-tetrahydropyridine 
• 1384732-99-3 C₄H₄O₄*C₁₂H₁₅NO 
• 51019-43-3 (R)-(-)-O-acetylmandelic acid 

Downstream Products

• 1426125-45-2 tert-butyl N-benzyl-N-[(3R,4R)-3-hydroxypiperidin-4-yl]carbamate 
• 1334700-32-1 (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol 

Relevant academic research and scientific papers

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 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.

Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical relevance

Four synthetic strategies were evaluated towards the preparation of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over the relative and absolute stereochemistry of the 4,3-amino alcohol moiety. The first strategy employed a novel RhI catalyzed asymmetric hydrogenation, while two other strategies exploited the existing stereochemistry in 2-deoxy-d-ribose, and the fourth explored both biocatalytic and classical resolution techniques as a means to impart enantioenrichment to racemic intermediates en route to targeted structure (-)-1. The Royal Society of Chemistry 2012.