Réaction #1503632

Équation de réaction

piperazine

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

2,4-dichloroquinazoline

sodium hydride

→

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

Rendement 34.8%

Solvants

dioxane

dioxane

water

dimethylformamide

Conditions de réaction

Traitement

1. 1
   Températurecooling
2. 2
   workup.STIRRINGthe mixture is stirred at room temperature for 2 hours
3. 3
   Extractionextracted with ethyl acetate twice
4. 4
   Lavagethe extract is washed with water
5. 5
   Séchagedried over anhydrous sodium sulfate
6. 6
   Autreevaporated to dryness under reduced pressure
7. 7
   AutreThe resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform
8. 8
   Autremethanol=100:1, v/v) to give an oily substance
9. 9
   AutreThe 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
    Extractionextracted with chloroform
13. 13
    Séchagedried over anhydrous sodium sulfate
14. 14
    Autreevaporated to dryness under reduced pressure
15. 15
    AutreThe resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform

Mode opératoire

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).

Source