Hydrochloric Acid → 4-Hydroxy-8-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid methyl ester

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Reaction Steps

A mixture of 4-Hydroxy-8-iodo-isoquinoline-3-carboxylic acid methyl ester (7 mmol, 2.3 g), 4-methoxy-phenol (35 mmol, 4.39 g), Cs2CO3 (35 mmol, 11.42 g), 2,2,6,6-tetramethyl-heptane-3,5-dione (2.8 mmol, 0.59 mL), CuCl (7 mmol, 0.70 g), and anhydrous DMF (42 mL) was refluxed under nitrogen with stirring for 15 min. before it was poured into ethyl acetate (700 mL). Water (700 mL) and 5 N hydrochloric acid (5 mL) were added and the mixture was stirred for 15 min. The organic phase was then separated and washed with water (2×700 mL) before it was dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel using hexanes:EtOAc=75:25 as the eluent gave the title compound as a tan solid (234 mg); MS-(+)-ion: M+1=326.4.

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