反応 #64020

反応方程式

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

溶媒

tetrahydrofuran

反応条件

後処理

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
   抽出extracted with chloroform (3×75 ml)
6. 6
   乾燥The combined organic extracts are dried over anhydrous magnesium sulfate
7. 7
   その他the solvent removed under reduced pressure
8. 8
   その他The crude residue is flash-chromatographed on neutral silica gel
9. 9
   その他crystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
10. 10
    その他are obtained

実験手順

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.

出典