Trisodium citrate → 4-Phenylpyridine

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In a 1L 3-neck flask, equipped with a mechanical stirrer, were mixed phenyl magnesium chloride (96.1 mL; 192 mmol; 2.00M in THF) and lithium thiophenoxide (211 mL; 211 mmol; 1.00M THF) under a blanket of nitrogen. This mixture was heated to 60° C. for 1 h, and then cooled to 0-5° C. with an ice bath. In a separate 150 mL flask, nickel acetylacetonate (“anhydrous”; 0.617 g; 2.40 mmol; 0.025 equiv.) was dissolved under nitrogen in anhydrous THF (100 mL). To this green solution was added trimethylphosphine (4.8 mL; 4.80 mmol; 1.00M in toluene; 0.05 equiv.) forming a blue solution. After stirring for 10 min, solid 4-cyanopyridine (10.0 g; 96.1 mmol; 1 equiv.) was added to the catalyst mixture forming a green solution. This solution was added via addition funnel to the PhMgCl/PhSLi reaction solution at a rate which maintained the reaction temperature below 15° C. After the addition was complete, the reaction was heated at 60° C. for 2 h. The reaction was then allowed to cool to room temperature, and was poured into 1M aqueous sodium citrate (500 mL). The organic layer was separated and the aqueous layer extracted three times with MTBE (265 mL each). The combined organic phase was extracted three times with 2N aqueous HCl (250 mL each) and this combined aqueous extract was basified to pH≈12 with 1N aqueous NaOH. This mixture was then extracted three times with MTBE (330 mL each) and the combined organic phase was dried over anhydrous magnesium sulfate. After filtration of the drying agent, solvent was removed in vacuo leaving 14.1 g (91% yield) of 4-phenylpyridine as a light yellow solid. GC analysis of the product showed it to be >95% pure.

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