2-Bromo-5-methoxyphenol

3-methoxyphenol (10, 1.034 g, 96 percent, 8.0 mmol) was dissolved in DCM (160 mL) and N-bromosuccinimide (1.424 g, 8.0 mmol) was added slowly at maximum stirring rate. The solution was stirred at ambient temperature for 1 h and quenched with water. The inorganic layer was extracted twice with DCM, and the combined organic layers were dried over MgSO4. The solvents were removed in vacuo, and the residue was purified by flash chromatography (DCM/isohexane 2:1) to afford phenol 6 (1.290 g, 79 percent) as a white solid.To the solution of 33 A (9.8 g, 79 mmol, 1.0 eq) in DCM (100 mL) was added NBS (14.8 g, 82.9 mmol, 1.05 eq) in DCM (150 mL) dropwise at 0 °C. The reaction mixture was stirred at room temperature for 2 hours under nitrogen atmosphere before it was concentrated in vacuo to dryness. The residue was purified by flash chromatography on silica (PE EA = 20: 1 to 5: 1) to give 33B (10.2 g, 64percent).Step B - Synthesis of Compound Int-22b; To a suspension of 3-methoxyphenol (3.0 g, 24.18 mmol) and CFSynthesis of Compound Int-22bInt 22bTo a suspension of 3-methoxyphenol (3.0 g, 24.18 mmol) and CFA 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).(1)