Reaktion #64020

Reaktionsgleichung

water

5-(Hydroxymethyl)-3-(4-chlorophenyl)-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidine

sodium hydride

methyl iodide

→

5-(Methoxymethyl)-3-(4-chlorophenyl)-3-(1H-imidazol-1-yl-methyl)-2-methylisoxazolidine

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe resulting suspension is heated
2. 2
   Temperaturto reflux
3. 3
   workup.STIRRINGstirred for 20 hours
4. 4
   TemperaturUpon cooling to room temperature
5. 5
   Extraktionextracted with chloroform (3×75 ml)
6. 6
   TrocknenThe combined organic extracts are dried over anhydrous magnesium sulfate
7. 7
   Sonstigethe solvent removed under reduced pressure
8. 8
   SonstigeThe crude residue is flash-chromatographed on neutral silica gel
9. 9
   Sonstigecrystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
10. 10
    Sonstigeare obtained

Vorschrift

5-(Hydroxymethyl)-3-(4-chlorophenyl)-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidine (3: R1 =4-Cl, R2 =H) 2.50 g, 8 mmol) is added to a suspension of 1.32 g (24 mmol) of 50% by weight sodium hydride in 50 ml anhydrous tetrahydrofuran, at 0° C. under a nitrogen atmosphere. After stirring for 1 hour at 0° C., 1.28 g (9 mmol) of methyl iodide is added and the resulting suspension is heated to reflux and stirred for 20 hours. Upon cooling to room temperature, the reaction mixture is poured into 100 ml of water and then extracted with chloroform (3×75 ml). The combined organic extracts are dried over anhydrous magnesium sulfate and the solvent removed under reduced pressure. The crude residue is flash-chromatographed on neutral silica gel using chloroform-methanol (98:2 by volume) as eluent. Following crystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3) are obtained, mp 123°-126° C.

Quelle