Citric Acid → [3-(2-tert-Butyl-pyrimidin-4-yl)-6-chloro-1H-indol-5-yl]-[4-(4-fluorobenzyl)-piperidin-1-yl]-methanone

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Reaction Steps

Preparation of 3-acetyl-6-chloro-1H-indol-5-yl)[4-(4-fluorobenzyl)piperidin-1-yl]methanone. A mixture of 3-acetyl-6-chloro-1H-indole-5-carboxylic acid (0,098 g, 0.41 mmol) and carbonyldiimidazole (0.101 g, 0.62 mmol) in dimethylformamide (1.0 mL) was stirred at room temperature for 1.5 h under nitrogen. The reaction mixture was cooled in ice bath, added 4-(4-fluorobenzyl)piperidine hydrochloride (0.1 g, 0.45 mmol), and triethylamine (0.5 g). The resulting mixture was stirred at room temperature for 3 h under nitrogen, added 5% citric acid and extracted with ethyl acetate (2×10 mL). The combined organic extracts were washed with water, dried (MgSO4) and concentrated to dryness. The residue was purified by silica gel flash chromatography using 25% ethyl acetate in heptane to afford the title compound as a glassy substance (0.08 g, 47%), m/z 413 (M+H).

Provenance & Evidence