Sulfuric Acid → 6-Fluoro-7-bromoisoquinoline

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Reaction Steps

A reaction mixture of 3-bromo-4-fluorobenzaldehyde (1.70 g, 8.37 mmol) (Aldrich, Cat. #339547) and aminoacetaldehyde dimethyl acetal (0.917 mL, 8.37 mmol) (Aldrich, Cat. #121967) in toluene (17.0 mL) was stirred at r.t. overnight. The mixture was then added to sulfuric acid (10 mL) and phosphorus pentoxide (2.38 g, 8.37 mmol) at 160° C. The mixture was stirred at 160° C. for 1 h. After cooled to r.t., the mixture was poured onto crushed ice. The acidic mixture was adjusted to pH=8 by the careful addition of NaOH in water with stirring and external cooling. The basic mixture was extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-40%) to afford the desired product. Analytic LCMS (M+H)+: m/z=225.9/227.9.

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