Hydrochloric Acid → 4-(Methoxy-phenyl)-isoquinoline-5-Sulfonic Acid

Participants

Reaction Steps

Treat a solution of 7-bromo-isoquinoline-5-sulfonic acid (150.00 g, 0.520 mol) and 4-methoxyphenylboronic acid (90.87 g, 0.598 mol) in DMF (1,400 mL) and MeOH (375 mL) with 2M aqueous Na2CO3 (652 mL). Deoxygenate the resulting slurry 3× with N2, then add Pd(OAc)2 (2.33 g, 0.0104 mol) and dppb (5.54 g, 0.0130 mol). Heat the resulting reaction mixture at ˜70° C. for 3 hr, then allow to cool to room temperature overnight. Dilute the reaction mixture with H2O (4,000 mL) and adjust the pH to ˜pH 2 with 5N aqueous HCl. Allow the resulting slurry to stir at room temperature for 30 min, then recover the brown solid by vacuum filtration, washing with H2O and drying under vacuum filtration. Dissolve the brown solid in DMF (1,000 mL) and 2M aqueous Na2CO3 (650 mL) and filter the resulting solution through a pad of Celite®, washing with DMF (400 mL)/H2O (400 mL). Treat the filtrate with 5N aqueous HCl to adjust the pH to ˜pH 2. Allow the resulting slurry to stir at room temperature for 30 min, then recover the solid by vacuum filtration, washing with H2O and drying under vacuum filtration overnight. Dissolve the solid in DMF (1,000 mL) and 2M aqueous Na2CO3 (1,000 mL) again and treat the resulting solution with Celite® to create a slurry. Stir the resulting slurry at room temperature for 30 min, then filter through a pad of Celite®, washing with H2O. Treat the filtrate with 5N aqueous HCl to adjust the pH to ˜pH 2. Stir the resulting slurry at room temperature for 30 min, then recover the solid by vacuum filtration, washing with H2O and drying under vacuum filtration overnight. Crush the solid, then wash with EtOAc, drying under vacuum filtration overnight, followed by drying in a drying oven under reduced pressure at ˜35° C. to afford the title compound (136.79 g, 83% yield) as a yellow solid: TOF-MS [ES+; m/z] 316.0624/316.0643. Anal. Calcd. For C16H13NO4S: C, 60.94; H, 4.15; N, 4.44; S, 10.16. Found C, 60.76; H, 4.13; N, 4.50; S, 9.90.

Provenance & Evidence