반응 #64020

반응 방정식

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

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   온도the resulting suspension is heated
2. 2
   온도to reflux
3. 3
   workup.STIRRINGstirred for 20 hours
4. 4
   온도Upon cooling to room temperature
5. 5
   추출extracted with chloroform (3×75 ml)
6. 6
   건조The combined organic extracts are dried over anhydrous magnesium sulfate
7. 7
   기타the solvent removed under reduced pressure
8. 8
   기타The crude residue is flash-chromatographed on neutral silica gel
9. 9
   기타crystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
10. 10
    기타are obtained

실험 절차

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.

출처