Synthesis of Naproxen by Palladium Catalysis

Preparation of an analgesic drug Organometallic chemistry Palladium-catalyzed reaction Advanced laboratory experiment 

Some NSAIDs are sold as racemic mixtures. One coimnon example is ibuprofen, sold as Advil , and marketed by Pfizer. Typically, only a single enantiomer is pharmacologically active. In the case of ibuprofen, it is the (S)-enantiomer. The inactive (R)-enantiomer in racemic ibuprofen is converted by an isomerase enzyme in the gut into the active enantiomer. Ibuprofen is now available as single enantiomer in certain preparations that supposedly has improved therapeutic value. Naproxen has always been marketed as the single enantiomer. 

Notice in the structures shown above that the carboxylic acid, naproxen, has a plus sign of rotation while the sodium salt, sodium naproxen, has a minus sign of rotation when measured in a polarimeter. You should recall from your study of stereochemistry in your lecture course that a compound with (S) stereochemistry may have either a plus or a minus value in a polarimeter. Likewise, a compound with the (R) stereochemistry can have either a plus or minus value. 

In this experiment, you will be preparing the carboxylic acid, naproxen, rather than the sodium salt, sodium naproxen. As is often the case with pharmaceuticals. 

In this experiment we present a new process involving a palladium metal-catalyzed reaction sequence. While the process employed in this experiment is not competitive with the Roche/Syntex process, it provides an interesting use of an organometallic catalysis for instructional purposes. 

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Once the gas flow in the manifold is adjusted, one of the stopcocks on the manifold is opened, and the needle is inserted into a rubber septum on the reaction flask. The gas flow into the reaction flask is controlled with the stopcock on the manifold. Excess gas is vented through another syringe needle inserted into the rubber septum. Often the rate of bubbling observed in the Gas Exit Port will slow when the stopcock to the reaction flask is opened. The gas flow from the Gas Inlet Port will need to be increased in order to maintain bubbling in the Gas Exit Port. A complete description of the use of a gas manifold assembly is given in Experiment 59, Synthesis of Naproxen by Palladium Catalysis. 

Synthesis of Naproxen (Aleve ) by palladium catalysis Green Epoxidation of Chalcones Cyclopropanation of Chalcones... 

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