Synthesis of 2-aryl Propenoic Acid Esters for Producing Non-steriodal, Anti-inflammatory Drugs

Wisconsin Alumni Research Foundation (University of Wisconsin)
posted on 04/25/2008

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Naproxen, a potent and popular non-steroidal, anti-inflammatory drug (NSAID), is difficult to synthesize in an efficient and environmentally friendly manner because it is marketed in an optically pure form. Most technologies for manufacturing optically active compounds, such as naproxen, generate large amounts of toxic waste and result in low yields of the desired product. A more efficient means of producing naproxen has been proposed, but is not commercially feasible due to the high cost of creating 2-(6-methoxy-2-naphthyl)propenoic acid, a key intermediate. This invention provides an efficient, cost-effective and environmentally-friendly method for producing 2-(6-methoxy-2-naphthyl)propenoic acid ester, which can be used to make naproxen. It involves reacting an aryl aldehyde with an alkyldiazoacetate in the presence of a catalytic amount of either a Bronsted acid or a Lewis acid to yield a 2-aryl-3-hydroxy-propenoic acid ester. Reduction of the 2-aryl-3-hydroxy-propenoic acid ester generates a 2-aryl-propenoic acid ester, which can be converted to 2-aryl-propenoic acid and then to the desired NSAID.

• Cost effective – uses less expensive starting materials
• Environmentally friendly – less waste and no toxic byproducts
• Efficient – fewer steps in the synthetic route
• Can be used to make other 2-aryl substituted propenoic acid esters for production of a wide variety of NSAIDs
• Generates high yields of optically active compounds