Methyl 5-bromo-2,4-dimethoxybenzoate → 5-Bromo-2,4-dimethoxybenzyl alcohol

Temperature

0 °C

To a solution of methyl 5-bromo-2,4-dimethoxy-benzoate (5.137 g, 22.05 mmol) in tetrahydrofuran (60 mL) cooled to 0° C. was added lithium aluminum hydride (863 mg, 22.05 mmol) in several portions. At the end of addition, the reaction mixture was stirred at 0° C. for 15 min before the icebath was removed. The reaction was continued at room temperature for 48 h. It was cooled to 0° C. and water (˜5 mL) was carefully added to quench the excess lithium aluminum hydride. Sodium hydroxide (5% solution, 20 mL) was then added and the layers were separated after 2 h of stirring. The product was extracted with diethyl ether (2×100 mL). The organic layers were washed with sodium bicarbonate solution (1×10 mL), brine (1×10 mL) and dried over anhydrous sodium sulfate. The solid was 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 40% ethyl acetate in hexanes yielded (5-bromo-2,4-dimethoxy-phenyl)-methanol as off-white solids (3.743 g, 81%).

1. additionAt the end of addition
2. customwas removed
3. waitThe reaction was continued at room temperature for 48 h
4. temperatureIt was cooled to 0° C.
5. additionwater (˜5 mL) was carefully added
6. customto quench the excess lithium aluminum hydride
7. additionSodium hydroxide (5% solution, 20 mL) was then added
8. customthe layers were separated after 2 h
9. stirringof stirring
10. extractionThe product was extracted with diethyl ether (2×100 mL)
11. washThe organic layers were washed with sodium bicarbonate solution (1×10 mL), brine (1×10 mL)
12. dry with materialdried over anhydrous sodium sulfate
13. filtrationThe solid was filtered off
14. concentrationthe filtrate was concentrated in vacuo
15. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
16. washeluting with 40% ethyl acetate in hexanes

ORD record

ord-05ce2ed847924be691d7838dd1cf229e

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06617346B1