Hydrochloric Acid → Triethyl Phosphate

HRID 650269Notes

Reaction equation

HRID 650269 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:8]([O:10][CH2:11][CH3:12])=[O:9].[P:13]([O:20][CH2:21][CH3:22])([O:17][CH2:18][CH3:19])[O:14][CH2:15][CH3:16].Cl>C(#N)C.O.ClCCl>[CH2:11]([O:10][C:8]([N:1]1[CH:6]=[CH:5][CH:4]([P:13]([O:17][CH2:18][CH3:19])(=[O:20])[O:14][CH2:15][CH3:16])[CH:3]=[CH:2]1)=[O:9])[CH3:12].[P:13]([O:20][CH2:21][CH3:22])([O:17][CH2:18][CH3:19])([O:14][CH2:15][CH3:16])=[O:9]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 10928Ethyl chloroformateHCID 31215Triethyl phosphite

Product 2

HCID 6535Triethyl PhosphateHCID 15573726HCID 15573726, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

A solution of pyridine (16.1 L, 0.2 kmol) in acetonitrile (160 L) is cooled to −10° C. Ethyl chloroformate (19.1 L, 0.2 kmol) is added at such a rate that the temperature does not rise above 0° C. The suspension is then stirred at −10 to 0° C. for 2 hours to ensure complete N-acylation. The batch is cooled to −30° C., and triethyl phosphite (34.3 L, 0.2 kmol) is added at such a rate that the temperature does not rise above −20° C. (ranging from −30 to −20° C.). The solution is stirred in this range for 2 hours, and then warmed to ambient temperature over several hours (or overnight). The acetonitrile is stripped under Sihi vacuum to a temperature not exceeding 80° C. and the residual liquid is cooled to 30° C. Dichloromethane (140 L) is added, followed by a mixture of water (60 L) and concentrated HCl (10 L). The mixture is stirred at ambient temperature for 1 hour, and the lower organic phase is pumped to a separate vessel and washed with water (100 L). After pumping back to the original (water-washed) vessel, it is washed with 1% potassium carbonate solution and finally with water to neutrality. The dichloromethane is then stripped to leave crude (about 92% pure) diethyl N-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate containing about 5% 1,2-isomer and traces of triethyl phosphate (oxidation of corresponding phosphite). The yield is about 48.4 kg of a light yellow liquid which is stored under nitrogen because it is slightly unstable to air.

Workup

  1. customdoes not rise above 0° C
  2. temperatureThe batch is cooled to −30° C.
  3. customdoes not rise above −20° C.
  4. custom(ranging from −30 to −20° C.)
  5. stirringThe solution is stirred in this range for 2 hours
  6. temperaturewarmed to ambient temperature over several hours (or overnight)
  7. customexceeding 80° C.
  8. temperaturethe residual liquid is cooled to 30° C
  9. stirringThe mixture is stirred at ambient temperature for 1 hour
  10. customthe lower organic phase is pumped to a separate vessel
  11. washwashed with water (100 L)
  12. washAfter pumping back to the original (water-washed) vessel, it
  13. washis washed with 1% potassium carbonate solution and finally with water to neutrality

Sources & evidence

ORD record
ord-8bb7e122917148d7808d1685b66722a4
Source dataset
uspto-grants-2001_08
Patent number
US06271378B1

Reaction notes

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