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.

中文翻译：

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（-）-（3 R，4 R）-1-苄基-4-（苄基氨基）哌啶-3-醇的替代路线的选择和放大评估

描述了（-）-（3 R，4 R）-1-苄基-4-（苄基氨基）哌啶-3-醇（4）的高效，可扩展的合成。由吡啶和苄基氯制备的吡啶鎓盐的还原产生相应的四氢吡啶衍生物。两阶段的环氧化反应，然后用BnNH ₂将环氧化物开环，建立了氨基醇的区域化学结构，并用于设定胺和羟基之间的反式关系。然后通过与（R）-O-乙酰基扁桃酸形成盐来拆分所得的外消旋中间体。该过程产生了（-）- 4的O-乙酰扁桃酸盐 苄氯的总收率为27％。