Water → 2-{[2-(Benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a suspension of NaH (2.2 g, 54 mmol, 60% in oil) in dry DMF (20 mL) was added dropwise a solution of 8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate (1f, 8.0 g, 27 mmol) in dry DMF (40 mL) at 0° C. under N2. The mixture was stirred at 0° C. for 15 minutes. 2-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 8.5 g, 32.4 mmol) was added. The mixture was stirred at room temperature overnight. To the reaction mixture was added dropwise H2O (200 mL) carefully. The mixture was extracted with EtOAc (2×150 mL). The combined organic layers were washed with brine (4×200 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 3:1) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate (1g, 14 g, 99%) as yellow oil.

Provenance & Evidence