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Synthesis 2011(10): 1604-1608  
DOI: 10.1055/s-0030-1260019
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Preparation of 2-Fluoro-3-aminophenylboronates via Directed ortho-Metalation

Paul E. Zhichkina, Sergiy G. Krasutsky*a, Catherine M. Beera, W. Martin Rennellsa, Seung H. Leeb, Jin-Ming Xiongb
a Medicinal Chemistry Department, AMRI, 26 Corporate Circle, P.O. Box 15098, Albany, NY, 12212, USA
Fax: +1(518)5122079; e-Mail: sergiy.krasutsky@amriglobal.com;
b Gilead Sciences, Inc., 36 East Industrial Rd., Branford, CT 06405, USA
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Publication History

Received 15 January 2011
Publication Date:
27 April 2011 (online)

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Abstract

The aromatic amine in fluoroanilines was protected with 2,2,5,5-tetramethyl-1-aza-2,5-disila-cyclopentane (stabase) in order to direct metalation ortho to the fluorine. A series of novel 2-fluoro-3-aminophenylboronates were prepared after quenching the metalated intermediate with triisopropylborate and deprotection in situ. The presented method is convenient and scalable, because all of the synthetic steps use crude intermediates. Several transformations are carried out in the same pot, and the final boronates are easily purified crystalline materials.

Key words

boronates - metalation - regioselectivity - protecting groups - amines

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