反应 #64020

反应方程式

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

溶剂

tetrahydrofuran

反应条件

后处理

1. 1
   温度the resulting suspension is heated
2. 2
   温度to reflux
3. 3
   workup.STIRRINGstirred for 20 hours
4. 4
   温度Upon cooling to room temperature
5. 5
   萃取extracted with chloroform (3×75 ml)
6. 6
   干燥The combined organic extracts are dried over anhydrous magnesium sulfate
7. 7
   其他the solvent removed under reduced pressure
8. 8
   其他The crude residue is flash-chromatographed on neutral silica gel
9. 9
   其他crystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
10. 10
    其他are obtained

实验过程

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.

来源