Reacción #48506

Ecuación de reacción

tert-butyl (3-oxopropyl)carbamate

4-benzylpiperazin-1-amine

hydrochloric acid ethyl acetate

→

title compound

Rendimiento 47.0%

1-(4-Benzylpiperazin-1-yl)tetrahydropyrimidin-2(1H)-one

Rendimiento 47.0%

Disolventes

methanol

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaunder reflux for 3 hours
2. 2
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
3. 3
   workup.DISSOLUTIONAfter the residue was dissolved in methanol (60 mL)
4. 4
   workup.ADDITIONacetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added
5. 5
   ConcentraciónThe reaction mixture was concentrated under reduced pressure
6. 6
   Extracciónextracted with dichloromethane
7. 7
   SecadoThe organic layer was dried over anhydrous sodium sulfate
8. 8
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
9. 9
   OtroThe residue obtained
10. 10
    workup.STIRRINGby stirring at room temperature for 5 hours
11. 11
    FiltraciónThe precipitate was collected by filtration
12. 12
    Otrodried
13. 13
    workup.ADDITIONDBU (14.6 g) and CDI (7.8 g) were added
14. 14
    Temperaturathe mixture was heated
15. 15
    Temperaturaunder reflux for 15 hours
16. 16
    ConcentraciónThe reaction mixture was concentrated under reduced pressure
17. 17
    workup.ADDITIONthe residue was diluted with an aqueous sodium bicarbonate solution
18. 18
    Extracciónextracted with dichloromethane
19. 19
    SecadoThe extract was dried over anhydrous sodium sulfate
20. 20
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
21. 21
    OtroThe residue was purified by basic silica gel column chromatography (ethyl acetate)
22. 22
    Otrorecrystallized from diethyl ether

Procedimiento

A solution of tert-butyl (3-oxopropyl)carbamate (4.2 g) and 4-benzylpiperazin-1-amine (4.6 g) in methanol (60 mL) was heated under reflux for 3 hours, and the solvent was distilled off under reduced pressure. After the residue was dissolved in methanol (60 mL), acetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added thereto, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, made alkaline with 1N sodium hydroxide and potassium carbonate, and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained was dissolved in ethyl acetate (10 mL). and then a 4N hydrochloric acid-ethyl acetate solution (100 ml) was slowly added at 0° C., followed by stirring at room temperature for 5 hours. The precipitate was collected by filtration, dried, and then suspended in acetonitrile (200 mL). DBU (14.6 g) and CDI (7.8 g) were added thereto, and the mixture was heated under reflux for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with an aqueous sodium bicarbonate solution and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate), and recrystallized from diethyl ether to obtain the title compound (3.1 g, 46%) as white crystals.

Fuente