Methyl iodide → 2-Bromo-1-methoxy-4-(methoxymethyl)benzene

Participants

Reaction Steps

To a solution of (3-bromo-4-methoxy-phenyl)-methanol (500 mg, 2.304 mmol, example 28) in tetrahydrofuran (5 mL) cooled to 0° C. was added sodium hydride (70 mg, 2.765 mmol). After 5 min, methyl iodide (287 μL, 4.608 mmol) was added. The reaction was then stirred at room temperature for 30 min. Thin layer chromatography (KP-Sil™ 32-63 μm, 60 Å silica gel, 40% ethyl acetate in hexanes) showed a mixture of starting material and product (higher Rf spot). Additional sodium hydride (58 mg) and methyl iodide (0.287 μL) were added and the reaction mixture was stirred at room temperature for 12 h. Water (5 mL) was added to quench the excess sodium hydride and the product was extracted with diethyl ether (2×50 mL). The organic layers were washed with brine (1×5 mL) and dried over anhydrous sodium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 20% ethyl acetate in hexanes yielded 2-bromo-1-methoxy-4-methoxymethyl-benzene (467 mg, 88%).

Provenance & Evidence