(5-fluoro-2,3-dihydro-1-benzofuran-2-yl)-piperazin-1-ylmethanone

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 50 ml round-bottomed flask containing a solution of (5-fluoro-2,3-dihydro-benzofuran-2-yl)-piperazin-1-yl-methanone (76 mg, 0.30 mmol, 1.1 eq) in 30 ml of dichloromethane was added EDAC.HCl (76 mg, 0.40 mmol, 1.5 eq), HOBt (56 mg, 0.41 mmol, 1.5 eq), triethylamine (56 mg, 0.55 mmol, 2.0 eq), and [4-(4-Nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-acetic acid (100 mg, 0.28 mmol). The solution was stirred overnight at room temperature before diluting with 30 ml of water. The crude product was then extracted from the mixture using 3×30 ml of ethyl acetate. 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/dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 72 mg of the desired amide as a yellow solid (44%); 1H NMR (300 MHz, CDCl3): δ 8.04 (d, J=6.6 Hz, 1H), 6.95 (d, J=5.4, 1H), 6.83 (m, 2H), 6.66 (m, 2H), 5.43 (m, 1H), 4.25 (s, 1H), 3.75-3.95 (m, 4H), 3.27-3.80 (m, 8H), 2.12-2.22 (m, 4H), 1.50 (dd, J=7.8 Hz, 16.8 Hz, 2H), 1.31 (dd, J=7.8 Hz, 16.8 Hz, 2H). The crude product was then extracted from the mixture dried over magnesium sulfate filtered concentrated under vacuum The crude residue was purified by silica gel chromatography to elute concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 100 ml round-bottomed flask was added 4-(5-Fluoro-2,3-dihydro-benzofuran-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester (1.8 g, 5.1 mmol), 50 ml of dichloromethane, and 2 ml of trifluoroacetic acid. The solution was stirred at room temperature overnight. The solution was made basic with the addition of saturated aqueous sodium bicarbonate. The mixture was then extracted with 4×50 ml of dichloromethane. The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated under vacuum to afford 1.2 grams of the desired amine as a brown oil (94%). The mixture was then extracted with 4×50 ml of dichloromethane dried over magnesium sulfate filtered concentrated under vacuum