4-Bromo-3-methoxyphenol

White solid

To a stirred solution of 4-bromoresorcinol (3.0 g, 15.87 mmol) in dry acetone (60 mL) were added KA solution of 40.0 gm (322.2 mMol) 3-methoxyphenol in 1 L acetonitrile was cooled to 0° C. under a nitrogen atmosphere. To this cooled solution was added a solution of 57.35 gm (322.2 mMol) N-bromosuccinimide in 500 mL acetonitrile dropwise at a rate to maintain the temperature of the reaction mixture at 0° C. (approximately 2 hours). The reaction mixture was stirred at 0° C. for about 1 hour after the addition was complete and was then concentrated under reduced pressure. The residue was treated with carbon tetrachloride and the solid which formed was removed by filtration. The filtrate was concentrated under reduced pressure to provide a mixture of bromination isomers as a red oil.This oil was subjected to silica gel chromatography, eluting with a gradient system of hexane containing from 0-30percent ethyl acetate. Fractions containing the fastest eluting compound were combined and concentrated under reduced pressure to provide 18.1 gm (28percent) of 2-bromo-5-methoxyphenol as a clear liquid.A solution of 40.0 gm (322.2 mMol) 3-methoxyphenol in 1L acetonitrile was cooled to 0°C under a nitrogen atmosphere. To this cooled solution was added a solution of 57.35 gm (322.2 mMol) N-bromosuccinimide in 500 mL acetonitrile dropwise at a rate to maintain the temperature of the reaction mixture at 0°C (approximately 2 hours). The reaction mixture was stirred at 0°C for about 1 hour after the addition was complete and was then concentrated under reduced pressure. The residue was treated with carbon tetrachloride and the solid which formed was removed by filtration. The filtrate was concentrated under reduced pressure to provide a mixture of bromination isomers as a red oil. This oil was subjected to silica gel chromatography, eluting with a gradient system of hexane containing from 0-30percent ethyl acetate. Fractions containing the fastest eluting compound were combined and concentrated under reduced pressure to provide 18.1 gm (28percent) of 2-bromo-5-methoxyphenol as a clear liquid.1H-NMR(CDCl3): δ 7.31 (d, 1H), 6.6 (d, 1H), 6.41 (dd, 1H), 5.5 (s, 1H), 3.77 (s, 3H). Fractions containing the later eluting components were combined and concentrated under reduced pressure. This residue was subjected to silica gel chromatography, eluting with dichloromethane. Fractions containing substantially pure 4-bromo-5-methoxyphenol were combined and concentrated under reduced pressure to provide 24.1 gm (37percent) of a white crystalline solid (m.p. = 68-69°C).1H-NMR(CDCl3): δ 7.34 (d, 1H), 6.45 (d, 1H), 6.33 (dd, 1H), 4.9 (br s, 1H), 3.85 (s, 3H).Step 1 : 4-Bromo-3-methoxyphenolTo a solution of 3-methoxyphenol (12.4 g, 100 mmol) in acetonitrile (400 ml) was added solid N-bromosuccinimide (19.5 g, 110 mmol) in portions over 10 minutes. The mixture was stirred at room temperature for 18 hours. The mixture was concentrated in a rotary evaporator and the residue was treated with ether (70 ml). The insoluble material was filtered off. The filtrate was washed with water (40 ml) and the organic layer dried over magnesium sulfate and filtered. The filtrate was concentrated and the residue purified by flash chromatography on silica gel using 0-10percent ethyl acetate/heptane to give the title compound (2.4 g, 12percent).EXAMPLE 4G Example 4G

Molecular Weight:203.03
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:201.96294
Monoisotopic Mass:201.96294
Topological Polar Surface Area:29.5
Heavy Atom Count:10
Complexity:108
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes