Reaktion #95977

Reaktionsgleichung

4-hydroxyphenylglycine

Methyl alcohol

propylene oxide

4-ethylpiperazin-2,3-dione-1-ylcarbonyl chloride

bis-trimethylsilylacetamide

→

α-(4-ethylpiperazin-2,3-dione-1-ylcarbonylamino)-4-hydroxyphenylacetic acid

Ausbeute 40.0%

Lösungsmittel

THF

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONTo a suspension of 8.3 g
2. 2
   Sonstigeat 75° C. for 2.5 hours to form a solution
3. 3
   workup.ADDITION, were added to the reaction mixture
4. 4
   workup.STIRRINGafter stirring for 15 minutes the mixture
5. 5
   Sonstigewas evaporated to dryness
6. 6
   workup.DISSOLUTIONThe gummy residue was dissolved in a mixture of ethyl acetate-aqueous sodium bicarbonate
7. 7
   Sonstigethe aqueous layer was separated
8. 8
   Waschenwashed with ethyl acetate
9. 9
   Filtrationfiltered
10. 10
    Temperaturcooled to 0° C
11. 11
    SonstigeThe organic phase was separated
12. 12
    Waschenwash of the acidified aqueous phase
13. 13
    Trocknendried over sodium sulfate
14. 14
    SonstigeEvaporation of the dried organic phase
15. 15
    Sonstigegave 6.7 g

Vorschrift

To a suspension of 8.3 g. (50 mmole) of 4-hydroxyphenylglycine in 75 ml. of tetrahydrofuran were added 25 ml. of bis-trimethylsilylacetamide and the suspension was stirred at room temperature for 15 minutes and then at 75° C. for 2.5 hours to form a solution. The solution was cooled to 0° C. and 25 ml. of propylene oxide were added. Next a solution of 11 g. of 4-ethylpiperazin-2,3-dione-1-ylcarbonyl chloride in 100 ml. of THF was added and the reaction mixture was stirred for 1 hour at 0° C. and at room temperature for 4 hours. Methyl alcohol, 40 ml., were added to the reaction mixture and after stirring for 15 minutes the mixture was evaporated to dryness. The gummy residue was dissolved in a mixture of ethyl acetate-aqueous sodium bicarbonate and the aqueous layer was separated, washed with ethyl acetate, filtered, and cooled to 0° C. The cold solution was layered with 200 ml. of fresh ethyl acetate and the pH adjusted to pH 1.9 with concentrated hydrochloric acid. The organic phase was separated, combined with an ethyl acetate wash of the acidified aqueous phase and dried over sodium sulfate. Evaporation of the dried organic phase gave 6.7 g. (40% yield) of α-(4-ethylpiperazin-2,3-dione-1-ylcarbonylamino)-4-hydroxyphenylacetic acid.

Quelle