反応 #221012

反応方程式

Chloromethyl ethyl ether

imidazole

sodium hydride

→

1-ethoxymethyl-1H-imidazole

収率 90.0%

溶媒

dimethyl sulfoxide

反応条件

後処理

1. 1
   workup.STIRRINGThe reaction mixture is stirred for another 2 hour at 80° C.
2. 2
   温度cooled to room temperature
3. 3
   抽出extracted with dichloromethane (4×200 ml)
4. 4
   乾燥The combined organic extracts are dried over sodium sulfate
5. 5
   ろ過filtered
6. 6
   濃縮concentrated in vacuo
7. 7
   その他The residue is fresh chromatographed in hexane/ethyl acetate from 5:1 to 2:1

実験手順

To a solution of imidazole (10.0 g, 146.9 mmole) in 100 ml dimethyl sulfoxide at room temperature under nitrogen is added sodium hydride (6.46 g, 161.6 mmole). The solution is stirred at 80° C. for 2 hours. Chloromethyl ethyl ether (16.35 ml, 176.3 mmole) is added dropwise. The reaction mixture is stirred for another 2 hour at 80° C., cooled to room temperature, poured into 5% aqueous solution and extracted with dichloromethane (4×200 ml). The combined organic extracts are dried over sodium sulfate, filtered, concentrated in vacuo. The residue is fresh chromatographed in hexane/ethyl acetate from 5:1 to 2:1 to give 1-ethoxymethyl-1H-imidazole as a brown oil 1.68 g (90%) MS(ES+): (M+H)=127.0 To the solution of 1-ethoxymethyl-1H-imidazole (1.24 g, 0.98 mmole) in 3.92 ml anhydrous tetrahydrofuran at −78° C. is added n-butyllithium (1.6 M in hexane) over 5 minutes. Reaction mixture is stirred at −78° C. for 1.5 hour, then (1S,2E)-1-isopropyl-4-[methoxy(methyl)amino]-3-methyl-4-oxobut-2-enyl(methyl)carbamate (427 mg, 1.36 mmole) in 2 ml anhydrous tetrahydrofuran is added over 10 minutes. The reaction mixture is stirred at −78° C. for 1 hour. Then, it is warmed to room temperature, stirred for 1 hour at room temperature. The reaction mixture is diluted with dichloromethane/water. The organic layer is washed with 5% sodium bicarbonate, dried over sodium sulfate, filtered, concentrated in vacuo. The residue is fresh chromatographed in hexane/ethyl acetate from 3:1 to 1:1 to give light yellow oil: [4-(1-Ethoxymethyl-1H-imidazol-2-yl)-1-isopropyl-3-methyl-4-oxo-but-2-enyl]-methyl-carbamic acid tert-butyl ester (120 mg, 23%) MS(ES+): (M+H)=380.2

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