Реакция #64020

Уравнение реакции

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

Растворители

tetrahydrofuran

Условия реакции

Обработка

1. 1
   Температураthe resulting suspension is heated
2. 2
   Температураto reflux
3. 3
   workup.STIRRINGstirred for 20 hours
4. 4
   ТемператураUpon cooling to room temperature
5. 5
   Экстракцияextracted with chloroform (3×75 ml)
6. 6
   СушкаThe combined organic extracts are dried over anhydrous magnesium sulfate
7. 7
   Другоеthe solvent removed under reduced pressure
8. 8
   ДругоеThe crude residue is flash-chromatographed on neutral silica gel
9. 9
   Другоеcrystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
10. 10
    Другоеare obtained

Методика

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.

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