Reaktion #50030

Reaktionsgleichung

triethylamine

dimethyl sulfate

THF

methyl ester

(S)-Pyroglutamic Acid Methyl Ester

dimethyl sulfate

dimethyl sulfate

→

(S)-N-methyl-pyroglutamic Acid Methyl Ester

Lösungsmittel

diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturHeating
2. 2
   workup.ADDITIONdropped below 15%
3. 3
   TemperaturThe thick reaction mixture was then cooled to 25° C.
4. 4
   Sonstigedid not rise above 30° C
5. 5
   WaschenThe emulsion was washed with two 50 L portions of water
6. 6
   SonstigeThe ether layer was separated
7. 7
   Extraktionthe residue was extracted with ethyl acetate (60 l)
8. 8
   TrocknenThe combined organic layers were dried over Na2SO4
9. 9
   Sonstigeazeotroped with toluene until no more triethylamine
10. 10
    Temperaturrefluxed under nitrogen until the reaction
11. 11
    SonstigeThe solvents were evaporated under vacuum
12. 12
    workup.DISTILLATIONthe residue was distilled under high vacuum
13. 13
    Sonstigeto yield a colorless product

Vorschrift

The methyl ester compound from step 5a above (18.3 kg, 127.8 mol) and dimethyl sulfate (20.09 kg, 159.3 mol) were introduced into a reactor, and the mixture was heated to 60° C. under an N2 atmosphere. Heating was continued until the concentration of starting material dropped below 15%. An additional 6.25 kg (0.5 eq) of dimethyl sulfate was added with exothermic response. The thick reaction mixture was then cooled to 25° C., and a solution of triethylamine (16.12 kg) in diethyl ether (19.2 L) was added at such a rate that the temperature did not rise above 30° C. The emulsion was washed with two 50 L portions of water. The ether layer was separated, and the residue was extracted with ethyl acetate (60 l). The combined organic layers were dried over Na2SO4 and azeotroped with toluene until no more triethylamine remained in the residue. The residue was mixed with dimethyl sulfate (1.7 kg, 13.5 mol) and THF (70 L) and refluxed under nitrogen until the reaction was complete. The solvents were evaporated under vacuum, and the residue was distilled under high vacuum to yield a colorless product.

Quelle