4-Bromophenol → (2R)-1-(4-bromophenoxy)-4-(3-pyridyl)-2-butanol

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Reaction Steps

Solid 4-bromophenol (2.08 g) was added to a stirred suspension of sodium hydride (60%, 0.48 g) in dimethylformamide (30 ml) and the resulting solution stirred for 30 minutes. (2R)-2-(tert-butyldimethylsilyloxy)-4-(pyridin-3-yl)-1-butyl para-toluenesulfonate (4.35 g, Example 5d)) was added and the mixture stirred at 60° C. for 2 hours. After cooling the mixture was poured into water (50 ml) and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained was dissolved in acetonitrile (20 ml) and hydrofluoric acid (40% in water; 5 ml, CAUTION) was added. The mixture was stirred for 1 hour and then poured into a solution of saturated aqueous sodium hydrogencarbonate. The mixture was extracted with ethyl acetate and the combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained was purified by column chromatography over silica eluting with acetone:hexane (1:1) to give the sub-title compound as a solid (2.65 g).

Provenance & Evidence