A Scaleable Synthesis of Methyl 3-Amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate

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• 作者：Eric E. Boros ; Svetlana A. Burova ; Greg A. Erickson ; Brian A. Johns ; Cecilia S. Koble ; Noriyuki Kurose ; Matthew J. Sharp ; Elie A. Tabet ; James B. Thompson ; Matthew A. Toczko
• 刊名：Organic Process Research & Development
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：11
• 期：5
• 页码：899 - 902
• 全文大小：96K
• 年卷期：v.11,no.5(September 2007)
• ISSN：1520-586X

文摘

A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (1b), starting from 5-bromo-2-methoxypyridine (8) and 4-fluorobenzaldehyde (9), is described. Key steps in the process include lithium–bromine exchange of 8, addition of the resulting lithiate to aldehyde 9, regioselective nitration of pyridone 12, and Pd-catalyzed alkoxycarbonylation of bromopyridine 15b. Overall yield of the five-stage synthesis was 23%; intermediates 10, 12, 13, 15b, and final product 1b·HCl were isolated as filterable solids. Compounds 1a,b are important intermediates in the synthesis of 7-benzylnaphthyridinones (e.g., 2) and related HIV-1 integrase inhibitors.