3-Bromo-4-methoxybenzoic acid → (3-Bromo-4-methoxyphenyl)methanol

Temperature

0 °C

To a solution of 3-bromo-4-methoxy-benzoic acid (8 g, 34.62 mmol) in diethyl ether (120 mL) cooled to 0° C. was added lithium aluminum hydride (1.49 g, 38.08 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 12 h. It was cooled back to 0° C. and water (2-5 mL) was carefully added to quench the excess lithium aluminum hydride. Sodium hydroxide (5% solution, 5-10 mL) was then added and the layers were separated after 1 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 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 40% ethyl acetate in hexanes yielded (3-bromo-4-methoxy-phenyl)-methanol as a white solid (6.262 g, 83%).

1. additionAt the end of addition
2. customwas removed
3. waitThe reaction was continued at room temperature for 12 h
4. temperatureIt was cooled back to 0° C.
5. additionwater (2-5 mL) was carefully added
6. customto quench the excess lithium aluminum hydride
7. additionSodium hydroxide (5% solution, 5-10 mL) was then added
8. customthe layers were separated after 1 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 then 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-7aa8c6d4b3984d0dabf36f9a0e4f0436

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06617346B1