Reduction of an Enaminone: Synthesis of the Diamino Alcohol Core of Ritonavir

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• 作者：Anthony R. Haight ; Timothy L. Stuk ; Michael S. Allen ; Lakshmi Bhagavatula ; Michael Fitzgerald ; Steven M. Hannick ; Francis A. J. Kerdesky ; Jerome A. Menzia ; Shyamal I. Parekh ; Timothy A. Robbins ; David
• 刊名：Organic Process Research & Development
• 出版年：1999
• 出版时间：March 1999
• 年：1999
• 卷：3
• 期：2
• 页码：94 - 100
• 全文大小：138K
• 年卷期：v.3,no.2(March 1999)
• ISSN：1520-586X

文摘

The reduction of (5S)-2-amino-5-dibenzylamino-4-oxo-1,6-diphenylhex-2-ene was optimized for diastereoselectivity andoverall conversion to (2S,3S,5S)-5-amino-2-dibenzylamino-3-hydroxy-1,6-diphenylhexane (2a). A two-step reduction sequence is described wherein the enamine is reduced with aborane-sulfonate derivative followed by reduction of the resulting ketone with sodium borohydride. The desired 2a wasobtained with 84% diastereoselectivity and an acyclic 1,4stereoinduction ratio of 14:1. This methodology has been usedto produce multikilogram quantities of the diamino alcohol coreof Ritonavir and should be general to the synthesis of relateddiamino hydroxyethylene isosteres.