Reaktion #1503627

Reaktionsgleichung

trans-1,2-cyclopentanediol

2,4-dichloroquinazoline

sodium hydride

piperazine

→

4-[trans-(2-hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)quinazoline

Ausbeute 19.1%

Lösungsmittel

dimethylformamide

dioxane

ethyl acetate

dioxane

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooling
2. 2
   workup.STIRRINGthe mixture is stirred at room temperature for 1 hour and 20 minutes
3. 3
   Waschenwashed with water 6 times
4. 4
   TrocknenThe resulting ethyl acetate solution is dried over anhydrous magnesium sulfate
5. 5
   Sonstigeis evaporated to dryness under reduced pressure
6. 6
   Sonstigethe residue is briefly purified with medium pressure liquid column chromatography (eluent, chloroform)
7. 7
   Sonstigeto give an oily substance
8. 8
   SonstigeThe oily substance thus obtained
9. 9
   workup.STIRRINGwith stirring at 70° C.
10. 10
    workup.STIRRINGthe mixture is stirred at the same temperature for one hour and 10 minutes
11. 11
    Waschenwashed with water
12. 12
    Trocknendried over anhydrous magnesium sulfate
13. 13
    SonstigeThe resulting solution is evaporated to dryness under reduced pressure
14. 14
    Waschenthe residue is washed with acetone
15. 15
    Sonstigethe resulting crystals are recrystallized from acetone

Vorschrift

To a solution of trans-1,2-cyclopentanediol [manufactured by Aldrich Co., cf. J. Chem. Soc., 4026 (1952)] (5.39 g) and 2,4-dichloroquinazoline [cf. J. Am. Chem. Soc., 53, 3867 (1931)] (9.58 g) in dimethylformamide (50 ml) is added gradually 60% sodium hydride (in oil) (2.49 g) with stirring under ice-cooling, and the mixture is stirred at room temperature for 1 hour and 20 minutes. The reaction mixture is diluted with ethyl acetate and washed with water 6 times. The resulting ethyl acetate solution is dried over anhydrous magnesium sulfate and is evaporated to dryness under reduced pressure, and the residue is briefly purified with medium pressure liquid column chromatography (eluent, chloroform) to give an oily substance. The oily substance thus obtained is dissolved in dioxane (27 ml), and the mixture is slowly added dropwise to a solution of piperazine (9.67 g) in dioxane (36 ml) with stirring at 70° C., and the mixture is stirred at the same temperature for one hour and 10 minutes. The reaction mixture is diluted with ethyl acetate, washed with water, and dried over anhydrous magnesium sulfate. The resulting solution is evaporated to dryness under reduced pressure, and the residue is washed with acetone, and the resulting crystals are recrystallized from acetone to give 4-[trans-(2-hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)quinazoline (2.89 g) as crystals.

Quelle