Potassium bis(trimethylsilyl)amide → 2-{[2-(Benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of methyl 8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate (Cpd F, 92.0 mg, 0.310 mmol) and 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 97.1 mg, 0.371 mmol) in 1,4-dioxane (3 mL) was added KHMDS (308 mg, 1.54 mmol). The reaction mixture was heated at 100° C. for 1 hour. The solvent was removed under vacuum and the residue diluted with EtOAc (10 mL) and water (10 mL). The pH of the aqueous layer was adjusted to 3-4 using 1N HCl. The aqueous layer was extracted with EtOAc (25 mL) and the organic layer concentrated under vacuum. The residue was purified by column chromatography (silica gel, heptanes/EtOAc) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid (90a, 52 mg, 33% yield) as an oil.

Provenance & Evidence