Dimethyl Sulfate → Methyl (2S)-1-methyl-5-oxoprolinate

温度

60 °C

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.

1. temperatureHeating
2. additiondropped below 15%
3. temperatureThe thick reaction mixture was then cooled to 25° C.
4. customdid not rise above 30° C
5. washThe emulsion was washed with two 50 L portions of water
6. customThe ether layer was separated
7. extractionthe residue was extracted with ethyl acetate (60 l)
8. dry with materialThe combined organic layers were dried over Na2SO4
9. customazeotroped with toluene until no more triethylamine
10. temperaturerefluxed under nitrogen until the reaction
11. customThe solvents were evaporated under vacuum
12. distillationthe residue was distilled under high vacuum
13. customto yield a colorless product

ORDレコード

ord-fdbb4594a18c4b7c882440ebfca7694a

出典データセット

uspto-grants-1995_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05424444