4-Methoxybenzyl alcohol → 1,3-Dibromo-5-[(4-methoxyphenyl)methoxy]benzene

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Reaction Steps

1,3-dibromo-5-nitrobenzene (30.0 g, 107 mmol), freshly powdered potassium hydroxide (10.8 g, 192 mmol) and tetrabutylammonium bromide (3.42 g, 10.7 mmol) were dissolved in tetramethyl urea (TMU, 90 mL). A solution of p-methoxybenzyl alcohol (17.8 g, 128 mmol) in TMU (30 mL) was added drop-wise at room temperature over a period of 1 h. The mixture was stirred for 48 h at room temperature. The reaction mixture was poured on ice (160 g) and was extracted with tert-butylmethyl ether (4×200 mL). The combined organics were dried (MgSO4) and concentrated to give the crude product which was purified by FC (2.5 kg SiO2, AcOEt/heptane 1:9) to provide 29.6 g of 3,5-dibromo-1-p-methoxy-benzyloxybenzene which was not completely pure but which crystallized upon standing. The solid was taken up in methanol (27 mL) and the formed slurry was stirred at 60° C. for 10 min. The suspension was cooled to 0-5° C. and was then filtered. The filter cake was washed with cold methanol (2×15 mL) and dried to provide 28.1 g (71%) of 3,5-dibromo-1-p-methoxy-benzyloxybenzene as an off-white solid.

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