Development of a Novel Pd-Catalyzed N-Acyl Vinylogous Carbamate Synthesis for the Key Intermediate of ICE Inhibitor VX-765

详细信息    查看全文

• 作者：Gerald J. Tanoury ; Minzhang Chen ; Yong Dong ; Raymond E. Forslund ; Derek Magdziak
• 刊名：Organic Letters
• 出版年：2008
• 出版时间：January 17, 2008
• 年：2008
• 卷：10
• 期：2
• 页码：185 - 188
• 全文大小：109K
• 年卷期：v.10,no.2(January 17, 2008)
• ISSN：1523-7052

文摘

journals/orlef7/10/i02/figures/ol702532hn00001.gif" ALIGN="left" HSPACE=5>

A novel Pd-catalyzed coupling of Cbz-protected proline amide with 4-bromo-5-ethoxyfuran-2(5H)-one was developed for the synthesis of theP1-P2 unit (5) of VX-765. The process afforded quantitative coupling in the presence of water, providing a 1:1 mixture of 5 and its ethoxyepimer epi-5. Compound 5 was isolated as a single diastereomer via fractional crystallization, which was stereoselectively converted to 17 viahydrogenation, and subsequently transformed to VX-765. Nine examples of the Pd coupling are presented with yields ranging from 76-98%.