Réaction #64020

Équation de réaction

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

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Températurethe resulting suspension is heated
2. 2
   Températureto reflux
3. 3
   workup.STIRRINGstirred for 20 hours
4. 4
   TempératureUpon cooling to room temperature
5. 5
   Extractionextracted with chloroform (3×75 ml)
6. 6
   SéchageThe combined organic extracts are dried over anhydrous magnesium sulfate
7. 7
   Autrethe solvent removed under reduced pressure
8. 8
   AutreThe crude residue is flash-chromatographed on neutral silica gel
9. 9
   Autrecrystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
10. 10
    Autreare obtained

Mode opératoire

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.

Source