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

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%).

1. additiona mixture of starting material and product (higher Rf spot)
2. stirringthe reaction mixture was stirred at room temperature for 12 h
3. customto quench the excess sodium hydride
4. extractionthe product was extracted with diethyl ether (2×50 mL)
5. washThe organic layers were washed with brine (1×5 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationThe solid was then filtered off
8. concentrationthe filtrate was concentrated in vacuo
9. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
10. washeluting with 20% ethyl acetate in hexanes

ORD record

ord-b5275bc85cab402db851acb3af371266

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06617346B1