Pyridine → Pyridinium, 1-(ethoxycarbonyl)-, chloride

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Reaction Steps

A solution of pyridine (320 g, 4.05 mol) in acetonitrile (1600 mL) was cooled to −25° C. and treated with ethyl chloroformate (440 g, 4.05 mol) over about 0.75 hours, keeping the temperature below −15° C. A very thick slurry of the intermediate N-ethoxycarbonylpyridinium chloride salt was formed. This suspension was stirred at −30 to −15° C. for 2 hours. Triethyl phosphite (671.2 g, 4.04 mol) was then added over about 1 hour while keeping the temperature in the same range. A yellow solution results. This was allowed to warm to ambient temperature overnight and the solvent was distilled off under vacuum to a maximum temperature of 60° C. The residual oil was dissolved in dichloromethane (2000 mL) and stirred with a mixture of water (500 mL) and concentrated hydrochloric acid (20 mL) at ambient temperature for 3 hours. The phases were separated and the dichloromethane solution washed with water (500 mL) and then with a solution of 1 g potash in 500 mL water. The pH of this wash is checked after IS minutes agitation and if in the 6-8 range, the dichloromethane solution is water-washed again and the solvent is removed under vacuum to a temperature of 70° C. (oil-pump vacuum was used towards the end of the distillation) to leave 1144 g (98%) of diethyl N-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate (DHP-Phosphonate). This material was a 91:9 mixture of DHP-Phosphonate and its 1,2-isomer.

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