Dimethyl Sulfate → 3,6,7-Trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline

Participants

Reaction Steps

To a solution of 6,7-dimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinolin-3-ol CCH 29038 free base (58 mg, 161 μmol) in dry DMF (6 mL) at 0° C. in a 25 mL round-bottomed flask equipped with a magnetic stirrer was added LiHMDS (1.0 N in TBME, 175 μL, 175 μmol) and the mixture was stirred for 20 min at RT. Dimethyl sulphate (18 μL, 192 μmol) was then added at 0° C. and the mixture was stirred overnight at RT. The mixture was then concentrated to dryness at 40° C. under vacuum and the residue was taken up in CH2Cl2 (40 mL). The organic solution was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 86:14) provided 23 mg of 3,6,7-trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline. 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 0.50 M HCl solution in MeOH (0.4 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 3,6,7-trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline hydrochloride 18 as a brown solid (25 mg, 38% yield).

Provenance & Evidence