Benzene → 4-(Diethoxyphosphorylmethyl)pyridine

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-chloropyridine hydrochloride (3.28 g, 20 mmol) in benzene (50 mL) was added 40% NaOH (1.35 mL). The resulting mixture was sonicated for 10 min and filtered. The residue was treated with additional benzene (15 mL), sonicated and filtered. The combined benzene layers were dried (Na2SO4) to give a solution of 4-chloropyridine which was used without further characterization (vida infra). A solution of diethyl phosphate (3.03 g, 22 mmol) in benzene (35 mL) was treated with freshly cut Na (510 mg, 22 mmol). The resulting mixture was refluxed for 30 min (oil temp. 90° C.), cooled to 0° C., then treated added dropwise over 10 min. with the solution of 4-chloropyridine in benzene (prepared as described above). After addition, the resulting mixture was refluxed for 3 h (oil temp. 100° C.) under argon then cooled to rt. The insoluble white precipitate was removed by filtration and rinsed with benzene (20 mL). The combined filtrate was concentrated and dried under high vacuum to give 3.5 g of diethyl pyridin-4-ylmethylphosphonate as a colorless liquid.

Provenance & Evidence