Toluene → 6-Chloropyridine-3-carbaldehyde

Participants

Reaction Steps

Corey, E. J.; Loh, T-P.; Achyutha Rao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. In a flame-dried flask under nitrogen a solution of 6-Chloro-N-methoxy-N-methyl-nicotinamide (5 g, 25 mmol) in tetrahydrofuran (50 mL) was cooled in an ice bath. A 1.5 M solution of diisobutylaluminum hydride in toluene (24.9 mL, 37 mmol) was added at a rate keeping the internal temperature of the reaction below 20° C. The reaction then stirred for 3 hours at room temperature. The completed reaction was cooled in an ice bath and carefully quenched with 1N hydrochloric acid. Stirring continued for 15 minutes more without the ice bath. The reaction mixture was extracted with ethyl acetate; the extracts were washed with brine, dried over magnesium sulfate, filtered and the filtrate was concentrated in vacuo to yield a yellow solid (3.3 g). The solids were dissolved in ether and filtered through diatomaceous earth to remove some insoluble material. The filtrate was diluted with hexanes and petroleum ether and the named compound was allowed to crystallize out over night. The precipitate was collected and dried (850 mg, 24%). Melting point 77-78° C. Second crop was collected and dried (375 mg, 11%).

Provenance & Evidence