反応 #50030

反応方程式

triethylamine

dimethyl sulfate

THF

methyl ester

(S)-Pyroglutamic Acid Methyl Ester

dimethyl sulfate

dimethyl sulfate

→

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

溶媒

diethyl ether

反応条件

後処理

1. 1
   温度Heating
2. 2
   workup.ADDITIONdropped below 15%
3. 3
   温度The thick reaction mixture was then cooled to 25° C.
4. 4
   その他did not rise above 30° C
5. 5
   洗浄The emulsion was washed with two 50 L portions of water
6. 6
   その他The ether layer was separated
7. 7
   抽出the residue was extracted with ethyl acetate (60 l)
8. 8
   乾燥The combined organic layers were dried over Na2SO4
9. 9
   その他azeotroped with toluene until no more triethylamine
10. 10
    温度refluxed under nitrogen until the reaction
11. 11
    その他The solvents were evaporated under vacuum
12. 12
    workup.DISTILLATIONthe residue was distilled under high vacuum
13. 13
    その他to yield a colorless product

実験手順

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.

出典