Methanol → Methyl 5-oxo-L-prolinate

HRID 440079Notes

Reaction equation

HRID 440079 reaction equation
CO.[NH:3]1[C:7](=[O:8])[CH2:6][CH2:5][C@H:4]1[C:9]([OH:11])=[O:10].OS(O)(=O)=O.[O-]S([O-])(=O)=O.[Na+].[Na+].[C:24]([O-])(O)=O.[Na+]>>[CH3:24][O:10][C:9](=[O:11])[C@@H:4]1[CH2:5][CH2:6][C:7](=[O:8])[NH:3]1

Participants

6

Reactant 5

HCID 887MethanolHCID 1118Sulfuric AcidHCID 7405L-Pyroglutamic Acid2×HCID 24436Sodium SulfateHCID 516892Sodium Bicarbonate

Product 1

HCID 78646Methyl 5-oxo-L-prolinate

Conditions

Temperature
60 °C

Procedure

Methanol (62 L, 1.155 mol), L-pyroglutamic acid (20 kg, 154.9 mol) and H2SO4 (97%, 0.87 L, 15.5 mol) were introduced into a reactor. The suspension was warmed to 60° C. and stirred until the pyroglutamic acid concentration dropped below 10%. The temperature of the reactor jacket was lowered to 0° C., and when the internal temperature reached 30° C., 9.7 kg (68.1 mol) of Na2SO4 was added and stirred for 15 min, then 8.1 kg (96.4 mol) of NaHCO3 was added. When pH 7 was reached (about 10 min), the suspension was filtered over a pad of celite. The filtrate was reintroduced into the reactor, and the methanol was distilled off at a pressure of 90-160 mbar and a jacket temperature of 50° C. Ethyl acetate (53 L) was then added with stirring, the mixture cooled to 0° C., and the mixture stirred for 16 hr. Unreacted pyroglutamic acid crystallized out and was removed by filtration. Removal of the ethyl acetate by evaporation under reduced pressure provided the title product as a viscous yellow oil, which was taken to the next step without further purification.

Workup

  1. additiondropped below 10%
  2. customwas lowered to 0° C.
  3. customreached 30° C.
  4. custom(about 10 min)
  5. filtrationthe suspension was filtered over a pad of celite
  6. additionThe filtrate was reintroduced into the reactor
  7. distillationthe methanol was distilled off at a pressure of 90-160 mbar
  8. customa jacket temperature of 50° C
  9. additionEthyl acetate (53 L) was then added
  10. stirringwith stirring
  11. temperaturethe mixture cooled to 0° C.
  12. stirringthe mixture stirred for 16 hr
  13. customUnreacted pyroglutamic acid crystallized out
  14. customwas removed by filtration
  15. customRemoval of the ethyl acetate
  16. customby evaporation under reduced pressure

Sources & evidence

ORD record
ord-507011164f73415e9c192538c06f5ecb
Source dataset
uspto-grants-1996_05
Patent number
US05516912

Reaction notes

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