Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

1455091-06-1

1455091-10-7

General procedure for the synthesis of methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate from methyl 2-[(methoxycarbonylmethyl)(toluene-4-sulfonyl)amino]methyl-4-phenoxybenzoate: a solution was prepared by dissolving sodium methanolate (12.70 g, 234.60 mmol) in methanol (40 mL) under ice-bath conditions. The solution was slowly added dropwise to a solution of dimethyl sulfoxide (82 mL) containing methyl 2-[(methoxycarbonylmethyl)(toluene-4-sulfonyl)amino]methyl-4-phenoxybenzoate (18.90 g, 39.10 mmol). After dropwise addition, the reaction mixture was continued to be stirred at room temperature for 2 hours. Upon completion of the reaction, methanol was removed by distillation under reduced pressure. The residue was diluted with water (50 mL) and the pH was adjusted to 10 with 1 N dilute hydrochloric acid.Subsequently, the organic layers were combined by extraction with ethyl acetate (100 mL x 3). The organic layer was washed sequentially with water (100 mL) and saturated brine (100 mL) and then dried with anhydrous sodium sulfate. The dried organic phase was concentrated under reduced pressure, and the resulting concentrate was separated and purified by column chromatography, resulting in 9.1 g of white solid product in 78.8% yield.