T. J. Connolly, Michael W. Disharoon, V. Dragan
Oct 21, 2010
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Organic Process Research & Development
Abstract
Enol ethers derived from 2-bromomalonaldehyde are useful intermediates for the preparation of functionalized imidazolecarboxaldehydes. Recent work in our group required that bromomalonaldehyde be converted to an enol ether on a large scale and be used in a campaign to generate a late-stage intermediate in the synthesis of an investigational active pharmaceutical ingredient (API). 2-Bromomalonaldehyde was converted into several enol ethers and each was evaluated with respect to its suitability for long-term storage and the temperature at which thermal decomposition was initiated. Although the highest onset temperature was measured with the ethyl enol ether (178 °C), the cyclohexyl enol ether was discovered to be an isolable solid (mp 66.5 °C). Other enol ethers examined in our hands could not be isolated as solids and storage as stock solutions did not offer the long-term stability required to support our campaign. A process safety hazards analysis revealed that the most potential for a hazardous event to ...