Methyl iodide → 1-Bromo-4-chloro-2-fluoro-3-methoxybenzene

Temperature

85 °C

To a stirred solution of 3-bromo-6-chloro-2-fluorophenol (4.2 g, 18.63 mmol) in acetonitrile (35 mL) was added potassium carbonate (5.15 g, 37.3 mmol) followed by methyl iodide (2.330 mL, 37.3 mmol) dropwise at rt. The reaction mixture was heated to 85° C. for 3 h. After cooling, the volatiles were concentrated under reduced pressure and the residue was diluted with water (50 mL) and extracted with ethyl acetate (2×80 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 1-bromo-4-chloro-2-fluoro-3-methoxybenzene (4 g, 16.7 mmol, 90% crude yield) as a brown solid. The material was carried forward without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 7.2 (m, 1H), 7.04 (m, 1H), 3.98 (s, 3H).

1. temperatureAfter cooling
2. concentrationthe volatiles were concentrated under reduced pressure
3. additionthe residue was diluted with water (50 mL)
4. extractionextracted with ethyl acetate (2×80 mL)
5. washThe combined organic layers were washed with brine (100 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-82e7be441a174ab89c42fb716bfb9711

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901305B2