Preparation of 5-(2-Methoxy-4-nitrophenyl)oxazole: A Key Intermediate for the Construction of VX-497
Organic Process Research & Development2002Vol. 6(5), pp. 677–681
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Abstract
A process for the multigram preparation of 5-(2-methoxy-4-nitrophenyl)oxazole, a key intermediate for the preparation of the hepatitis C drug candidate VX-497 (merimepodib), has been achieved in good yield from a commercially available dye. Early studies focused on the preparation of the requisite aldehyde by the Beech reaction. A second approach utilized a palladium (0)-catalyzed formylation of an aryl diazonium species, which was followed by condensation of the aldehyde with tosylmethyl isocyanide (TosMIC) to provide the required oxazole. This two-step method has been carried out to provide multigram samples of this key intermediate in 75% overall yield and >95% purity from the commercially available Fast Red B tetrafluoroborate salt.
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