Methanol → Methyl 5-oxo-L-prolinate

Temperature

60 °C

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.

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

ORD record

ord-bcac725e8d74422aad39a80a0f9d319a

Source dataset

uspto-grants-1995_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05424444