Concise Synthesis of (2S,3R)-3-Hydroxy-2-phenylpiperidine: An AdvancedKey Intermediate of Human Non-Peptide NK-1 Receptor Antagonists

摘要

The rapid, high-yielding synthesis of (2S,3R)-3-hy-droxy-2-phenylpiperidine, a known advanced key intermediate ofsome non-peptide human NK-1 receptor antagonists such as (+)-CP-99,994, (+)-CP-122,721 and (+)-LP-733,060, is reported. Thissynthesis involves the stereoselective addition of racemic 3-(meth-oxymethoxy)allenylzinc bromide to enantiopure (Rs,E)-N-2-ben-zylidene-2-methylpropane-2-sulfinamide and a ring-closingmetathesis reaction as the key steps. Following this procedure,(2S,3R)-3-hydroxy-2-phenylpiperidine is obtained in seven steps in56.2% overall yield.