Triethylamine → 4-(5-Fluoro-2,3-dihydro-benzofuran-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester

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Reaction Steps

In a 250 ml round-bottomed flask containing a solution of 5-fluoro-2,3-dihydro-benzofuran-2-carboxylic acid (1.8 g, 9.9 mmol) in 100 ml of dichloromethane was added EDAC.HCl (2.85 g, 14.9 mmol, 1.5 eq), HOBt (2.00 g, 14.8 mmol, 1.5 eq), triethylamine (2.00 g, 19.8 mmol, 2.0 eq), and t-butyl piperazine-1-carboxylate (2.20 g, 11.8 mmol, 1.2 eq). The solution was stirred overnight at room temperature before diluting with 50 ml of water. The crude product was then extracted from the mixture using 3×50 ml of dichloromethane. The organic layers were combined, dried over magnesium sulfate, filtered, and then concentrated under vacuum. The crude residue was purified by silica gel chromatography using ethyl acetate/petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1.8 grams of the desired amide as a light yellow solid (52%); 1H NMR (300 MHz, CDCl3): δ 6.92 (dd, J=2.4 Hz, 7.8 Hz, 1H), 6.79 (m, 1H), 6.69 (dd, J=4.2 Hz, 8.7 Hz, 1H), 5.40 (dd, J=7.2 Hz, 9.9 Hz, 1H), 3.78-3.91 (m, 3H), 3.46-3.67 (m, 5H), 3.26-3.39 (m, 2H), 1.49 (s, 1H).

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