Réaction #1503627

Équation de réaction

trans-1,2-cyclopentanediol

2,4-dichloroquinazoline

sodium hydride

piperazine

→

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

Rendement 19.1%

Solvants

dimethylformamide

dioxane

ethyl acetate

dioxane

ethyl acetate

Conditions de réaction

Traitement

1. 1
   Températurecooling
2. 2
   workup.STIRRINGthe mixture is stirred at room temperature for 1 hour and 20 minutes
3. 3
   Lavagewashed with water 6 times
4. 4
   SéchageThe resulting ethyl acetate solution is dried over anhydrous magnesium sulfate
5. 5
   Autreis evaporated to dryness under reduced pressure
6. 6
   Autrethe residue is briefly purified with medium pressure liquid column chromatography (eluent, chloroform)
7. 7
   Autreto give an oily substance
8. 8
   AutreThe 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
    Lavagewashed with water
12. 12
    Séchagedried over anhydrous magnesium sulfate
13. 13
    AutreThe resulting solution is evaporated to dryness under reduced pressure
14. 14
    Lavagethe residue is washed with acetone
15. 15
    Autrethe resulting crystals are recrystallized from acetone

Mode opératoire

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.

Source