Thursday, 26 June 2014

Acid-Facilitated Debenzylation of N-Boc, N-Benzyl Double Protected 2-Aminopyridinomethylpyrrolidine Derivatives

Tetrahedron. Author manuscript; available in PMC Feb 4, 2013.

Published in final edited form as:

Tetrahedron. Feb 4, 2012; 68(5): 1359–1366.

Published online Dec 13, 2011. doi: 10.1016/j.tet.2011.12.013

PMCID: PMC3358821

NIHMSID: NIHMS344972

Acid-Facilitated Debenzylation of N-Boc, N-Benzyl Double Protected 2-Aminopyridinomethylpyrrolidine Derivatives

Haitao Ji,^1,² Qing Jing,¹ Jinwen Huang,^1,³ and Richard B. Silverman^1,^*

Author information ► Copyright and License information ►

The publisher's final edited version of this article is available at Tetrahedron

Abstract

2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu reaction of a naphthol and a hindered secondary alcohol were optimized to give good to excellent yields. A key step in the synthesis of these inhibitors is the deprotection of the benzyl group from the N-Boc and N-Bn double protected 2-aminopyridine ring at a late stage of the synthesis, which has been proven difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn deprotection.

Keywords: 2-Aminopyridinomethyl pyrrolidines, Mitsunobu reaction, N-Benzyl deprotection, Palladium-catalyzed hydrogenation