Reacción #41540

Ecuación de reacción

acetic anhydride

p-toluenesulfonic acid monohydrate

t-butyl 2-(5-ethoxycarbonyl-2-methoxymethoxy-phenyl)-pyrrolidine-1-carboxylate

sodium bicarbonate

acetic anhydride

potassium carbonate

acetic anhydride

→

compound

ethyl 3-(1-acetyl-pyrrolidin-2-yl)-4-hydroxybenzoate

Disolventes

pyridine

ethanol

water

pyridine

water

methanol

triethylamine

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe reaction liquid
2. 2
   Temperaturawas heated
3. 3
   Temperaturaunder reflux for 2 days
4. 4
   TemperaturaAfter cooled
5. 5
   Otrothe reaction liquid
6. 6
   Extracciónextracted with a mixed solvent of chloroform/methanol (10/1)
7. 7
   Secadodried with anhydrous magnesium sulfate
8. 8
   OtroThe solvent was evaporated away under reduced pressure
9. 9
   Otroto obtain a crude product
10. 10
    workup.WAITFurther after 1 hour
11. 11
    workup.WAITfurther after 40 minutes
12. 12
    workup.WAITFurther after 30 minutes
13. 13
    Otrothe reaction liquid
14. 14
    workup.STIRRINGwas stirred for 30 minutes
15. 15
    OtroThe reaction liquid
16. 16
    Lavadowashed with aqueous saturated sodium bicarbonate
17. 17
    Extracciónthe aqueous layer was extracted with ethyl acetate
18. 18
    SecadoThe combined organic layers were dried with anhydrous magnesium sulfate
19. 19
    Otrothe solvent was evaporated away under reduced pressure
20. 20
    Otroto obtain a crude product
21. 21
    Otrothe reaction liquid
22. 22
    workup.STIRRINGwas stirred for 4 hours at room temperature
23. 23
    OtroThe reaction liquid
24. 24
    workup.DISTILLATIONwas distilled under reduced pressure
25. 25
    workup.ADDITIONthe resulting residue was diluted with aqueous saturated ammonium chloride solution
26. 26
    Extracciónextracted with ethyl acetate
27. 27
    SecadoThis was dried with anhydrous magnesium sulfate
28. 28
    Otrothe solvent was evaporated away under reduced pressure
29. 29
    Filtraciónthe resulting solid was taken out through filtration with ethyl acetate

Procedimiento

13 g of p-toluenesulfonic acid monohydrate was added to a solution of 26 g of t-butyl 2-(5-ethoxycarbonyl-2-methoxymethoxy-phenyl)-pyrrolidine-1-carboxylate in a mixture of 250 ml of ethanol and 50 ml of water, and the reaction liquid was heated under reflux for 2 days. After cooled, the reaction liquid was diluted with water, neutralized with aqueous sodium bicarbonate, extracted with a mixed solvent of chloroform/methanol (10/1), and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain a crude product. 13 ml of acetic anhydride was added to a pyridine (200 ml) solution of the resulting crude product, and stirred. After 1 hour, 6 ml of acetic anhydride was added to it. Further after 1 hour, 150 ml of pyridine was added to it, and further after 40 minutes, 5 ml of triethylamine was added thereto. Further after 30 minutes, 3 ml of acetic anhydride was added to it, and the reaction liquid was stirred for 30 minutes. The reaction liquid was diluted with ethyl acetate, and washed with aqueous saturated sodium bicarbonate, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure to obtain a crude product. 10 g of potassium carbonate was added to a methanol (200 ml) solution of the resulting crude product, and the reaction liquid was stirred for 4 hours at room temperature. The reaction liquid was distilled under reduced pressure, and the resulting residue was diluted with aqueous saturated ammonium chloride solution, and extracted with ethyl acetate. This was dried with anhydrous magnesium sulfate, then the solvent was evaporated away under reduced pressure, and the resulting solid was taken out through filtration with ethyl acetate to obtain the entitled compound as a white solid.

Fuente