Hydrochloric Acid → 1-(4-Isopropoxyphenyl)-5-(5-trifluoromethylpyridin-2-yl)indole-2,3-dicarb-oxylic acid diethyl ester

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Reaction Steps

t-BuLi (1.5 M in pentane, 4.5 mL, 3 mmol) was added dropwise at −78° C. to Et2O (15 mL). 2-Bromo-5-trifluoromethylpyridine (762 mg, 3.37 mmol) in Et2O (5 mL) was added via syringe. After 20 min at −78° C. the cold mixture was cannulated to cooled (−78° C.) ZnCl2 (1 M in Et2O, 7.4 mL, 7.4 mmol). The mixture was allowed to warm to rt and was stirred at rt for 3 h. The mixture was diluted with THF (15 mL) and added to a mixture of 5-bromo-1-(4-isopropoxyphenyl)indole-2,3-dicarboxylic acid diethyl ester (800 mg 1.69 mmol, see step (c) above), Pd(dppf)Cl2 (165 mg, 0.20 mmol), CuI (77 mg, 0.40 mmol) and NT-methylpyrrolidin-2-one (5.3 mL). The mixture was heated at 80° C. for 6 h, poured into NH4Cl (aq, sat, 50 mL) and extracted with t-BuOMe (3×30 mL). The combined extracts were washed with brine, dried (Na2SO4) and filtered through Celite®. The solids were washed with t-BuOMe and the combined filtrates were concentrated. The residue was dissolved in anhydrous Et2O and HCl (4 M in dioxane, 500 μL, 2.0 mmol) was added. After 10 min the mixture was concentrated and the residue was treated with anhydrous Et2O to give the sub-title compound. Yield 900 mg (92%).

Provenance & Evidence