Cyano-Substituted 2-Carboxyimidazoles:
Synthesis of 4-Cyano-1-{[2-(tri­meth­ylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate Potassium Salt

Mark J. Wall; Carsten Schubert; Carl R. Illig

doi:10.1055/s-0028-1083173

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Synthesis 2008(21): 3377-3379
DOI: 10.1055/s-0028-1083173

SHORTPAPER

Cyano-Substituted 2-Carboxyimidazoles: Synthesis of 4-Cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate Potassium Salt

Mark J. Wall*, Carsten Schubert, Carl R. Illig
Johnson and Johnson Pharmaceutical Research and Development, LLC, 665 Stockton Drive, Exton, PA 19031, USA
Fax: +1(610)4588249; e-Mail: mwall2@prdus.jnj.com;

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Publication History

Received 30 May 2008
Publication Date:
16 October 2008 (online)

Abstract
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Abstract

The first example of a monocyano-substituted 2-carboxyimidazole is reported. A synthesis of potassium 4-cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate (2) is demonstrated where the carboxylate group is introduced via bromine-magnesium exchange on a SEM-protected cyanoimidazole followed by reaction with ethyl cyanoformate. The synthesis includes the equilibration of a regioisomeric mixture of SEM-protected imidazoles to give a single product.

Key words

cyanoimidazole - bromine-magnesium exchange - carboxylation - protecting group migration

References

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8

Accession number CCDC 694823. Crystal data of 2: C₁₁H₁₆KN₃O₃Si, M = 305.46 g mol^-¹, colorless plates. Monoclinic space group P2₁/c, a = 20.8(4), b = 26.29(5), c = 11.52(2) Å, β = 96.24(3) ˚, V = 6263(2) Å^³, T = -180 ˚C, Z = 16, ρ_calcd = 1.296 g cm^-³, µ (Cu-Kα) = 3.781, multiscan, F(000) = 2560, 40580 reflections in h(-20/20), k(-13/26), l(-9/8) measured in the range 2.72˚ ≤ θ ≤ 50.95˚, completeness 88%, 5979 unique reflections, R _int = 0.0987, 4703 reflections with F _o > 4σ, 693 parameters, 0 restraints, R1_obs = 0.1365, wR2_obs = 0.3996, R1_all = 0.1595, wR2_all = 0.3996, GOOF = 1.544, largest difference peak and hole 2.41/-0.97 eÅ^-³.