Potassium Hydroxide → HCID 178486669, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (152 mg, 693 μmol) in toluene (15 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.38 mL, 0.76 mmol) at RT followed by 1-(bromomethyl)-4-phenoxybenzene (191 mg, 726 μmol) and the mixture was stirred at 140° C. for 50 min under microwave irradiation then at 160° C. for 50 min under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (10 mL) before extraction with EtOAc (50 mL). The organic phase was isolated and the aqueous phase was further extracted with CH2Cl2 (50 mL). Both organic phases were washed with brine (10 mL), combined, dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:3) gave 43 mg of 6,7-dimethoxy-1-methyl-4-(4-phenoxybenzyl)isoquinolin-3-ol. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.09 M HCl solution in MeOH (3 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-1-methyl-4-(4-phenoxybenzyl)isoquinolin-3-ol hydrochloride 5 as a brown solid (47 mg, 15% yield).

Provenance & Evidence