Reaktion #1503632

Reaktionsgleichung

piperazine

(1R,2R)-cyclopentane-1,2-diol

2,4-dichloroquinazoline

sodium hydride

→

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

Ausbeute 34.8%

Lösungsmittel

dioxane

dioxane

water

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooling
2. 2
   workup.STIRRINGthe mixture is stirred at room temperature for 2 hours
3. 3
   Extraktionextracted with ethyl acetate twice
4. 4
   Waschenthe extract is washed with water
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   Sonstigeevaporated to dryness under reduced pressure
7. 7
   SonstigeThe resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform
8. 8
   Sonstigemethanol=100:1, v/v) to give an oily substance
9. 9
   SonstigeThe oily substance thus obtained
10. 10
    workup.STIRRINGwith stirring at 70° C.
11. 11
    workup.STIRRINGthe mixture is stirred at the same temperature for one hour
12. 12
    Extraktionextracted with chloroform
13. 13
    Trocknendried over anhydrous sodium sulfate
14. 14
    Sonstigeevaporated to dryness under reduced pressure
15. 15
    SonstigeThe resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform

Vorschrift

To a solution of (1R,2R)-cyclopentane-1,2-diol [manufactured by Fluka Co.] (1.16 g) and 2,4-dichloroquinazoline (2.00 g) in dimethylformamide (40 ml) is added gradually 60% sodium hydride (in oil) (0.4 g) with stirring under ice-cooling, and the mixture is stirred at room temperature for 2 hours. The reaction mixture is poured into water and extracted with ethyl acetate twice, and the extract is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform:methanol=100:1, v/v) to give an oily substance. The oily substance thus obtained is dissolved in dioxane (20 ml), and the mixture is slowly added dropwise to a solution of piperazine (1.9 g) in dioxane (20 ml) with stirring at 70° C., and the mixture is stirred at the same temperature for one hour. The reaction mixture is poured into ice-water and extracted with chloroform. The extract is wished with water, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure. The resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform:methanol=20:1, 5:1, v/v) to give 4-[(1R,2R)-(2-hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)-quinazoline (1.1 g).

Quelle