Hydrogen Bromide → 2-Bromo-6-hydroxymethyl-3-[8(4-methoxyphenyl)octyloxy]pyridine hydrobromide

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Reaction Steps

The crude 2-bromo-3-hydroxy-6-hydroxymethylpyridine (vide supra, 1.12 mol) was dissolved in dimethyl formamide (1150 ml) at 60° C. 1-Chloro-8-(4-anisyl)-octane (342 g, 1.34 mmol) and potassium carbonate (388 g, 2.81 mol) were added. It was found to be important that the potassium carbonate was ground to as fine a powder as possible. The mixture was stirred vigorously and heated to 90°-95° C. until the assay of 2-bromo-3-hydroxy-6-hydroxymethylpyridine (by HPLC) fell below 3% (approx 5 h). The mixture was then cooled to room temperature, poured into water (10 L) and extracted with ethyl acetate (3×670 ml). The combined ethyl acetate extracts were washed with water (2×500 ml) and dried before being evaporated to dryness. The crude reaction product was dissolved in butan-1-ol (2700 ml) and hydrogen bromide gas (120 g) passed through the solution keeping the temperature below 70° C. After allowing the mixture to cool to 10° C. with vigorous stirring the solid product was filtered and washed with ethyl acetate (2×500 ml). The solid product was dried under vacuum at 60° C. for 4 days. Yield 421 g, 75%.

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