Dimethylformamide → Methyl 5-bromo-2,4-dimethoxybenzoate

Temperature

85 °C

To solution of 5-bromo-2,4-dihydroxy-benzoic acid (5 g, 21.46 mmol) in dimethylformamide (30 mL) were added dimethyl sulfate (5.413 g, 42.92 mmol) and potassium carbonate (8.907 g, 64.38 mmol). The reaction mixture was heated at 80-90° C. for 12 h. Upon cooling to room temperature, the white solid was filtered off and the filtrate was concentrated in vacuo. The product was extracted with diethyl ether (2×100 mL). The organic layers were washed with water (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 20-30% ethyl acetate in hexanes yielded methyl 5-bromo-2,4-dimethoxy-benzoate as a white solid (5.137 g, 87%).

1. temperatureUpon cooling to room temperature
2. filtrationthe white solid was filtered off
3. concentrationthe filtrate was concentrated in vacuo
4. extractionThe product was extracted with diethyl ether (2×100 mL)
5. washThe organic layers were washed with water (1×10 mL), brine (1×10 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationThe solid was 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 20-30% ethyl acetate in hexanes

ORD record

ord-d15fabd8fd1046cb8715bf4e51bbdd92

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06617346B1