Pyridine → HCID 15573725, compound

Temperature

-25 °C

A solution of pyridine (316 g, 4.0 mol) in acetonitrile (4.0 L) was cooled to 0° C. and ethyl chloroformate (434 g, 4.0 mol) was added over about 1.25 hours while keeping the temperature less than 5° C. The resulting yellow suspension was stirred at −5° C. to 0° C. for 1.5 hours. It was then cooled to −25° C. and trimethyl phosphite (496.3 g, 4.0 mol) was added over 1 hour, keeping the temperature less than −20° C. It was allowed to warm to ambient temperature overnight. The solvent was removed under reduced pressure at t<70° C. and the resulting oil was dissolved in dichloromethane (2.8 L) and washed with water (2 L) 5% HCl (2 L), 2% K2CO3 solution (1 L), and finally water (2 L) to pH neutrality. The solution was then concentrated under reduced pressure to a yellow oil (645 g, 62%) which by capillary GC was a 1:1 mixture of dimethyl N-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate and dimethyl N-ethoxycarbonyl-1,2-dihydropyridine-2-phosphonate. This material was used directly for the hydrogenation below, since attempted distillation leads to decomposition.

1. customthe temperature less than 5° C
2. customthe temperature less than −20° C
3. temperatureto warm to ambient temperature overnight
4. customThe solvent was removed under reduced pressure at t<70° C.
5. dissolutionthe resulting oil was dissolved in dichloromethane (2.8 L)
6. washwashed with water (2 L) 5% HCl (2 L), 2% K2CO3 solution (1 L), and finally water (2 L)
7. concentrationThe solution was then concentrated under reduced pressure to a yellow oil (645 g, 62%) which by capillary GC
8. additiona 1:1 mixture of dimethyl N-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate and dimethyl N-ethoxycarbonyl-1,2-dihydropyridine-2-phosphonate
9. distillationdistillation

ORD record

ord-f3176292bfc248f9872419c3f195a32b

Source dataset

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06271378B1