反应详情

温度

0 °C

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.

1. temperaturethe resulting suspension is heated
2. temperatureto reflux
3. stirringstirred for 20 hours
4. temperatureUpon cooling to room temperature
5. extractionextracted with chloroform (3×75 ml)
6. dry with materialThe combined organic extracts are dried over anhydrous magnesium sulfate
7. customthe solvent removed under reduced pressure
8. customThe crude residue is flash-chromatographed on neutral silica gel
9. customcrystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
10. customare obtained