Tetrahydrofuran → 1-(3-benzofuranyl)methylcarbonyl-4-(1H-indol-4-yl)piperazine

Participants

Reaction Steps

A mixture of 2-(3-benzofuranyl)acetic acid (0.95 g), 1-(1H-indol-4-yl)piperazine (1.3 g), and N,N-dicyclohexylcarbodiimide (1.3 g) in a mixture of dry tetrahydrofuran (50 mL) and dry dimethylformamide (10 mL) was stirred for 16 h at room temperature. Filtration and removal of solvent in vacuo gave an oil which was purified by flash chromatography (eluent: ethyl acetate/heptane/triethylamine 10:9:1) giving 1-(3-benzofuranyl)methylcarbonyl-4-(1H-indol-4-yl)piperazine (0.5 g) as an oil. The oil was dissolved in tetrahydrofuran (20 mL) and treated with a suspension of lithium aluminium hydride (0.26 g) in tetrahydrofuran (20 mL) at room temperature under a nitrogen atmosphere followed by reflux for 4 hours. The reaction mixture was cooled to 0° C. and treated subsequently with water (1 mL), 15% aq. sodium hydroxide (0.5 mL), and water (2.5 mL). After stirring for 30 min the mixture was filtered and concentrated. The remaining oil was dissolved in acetone followed by addition of oxalic acid and filtration, giving the title compound as a crystalline material (0.4 g). Mp 130-32° C. 1H NMR (DMSO-d6): 3.05-3.15 (m, 2H); 3.15-3.30 (m, 6H); 3.35 (s, 4H); 6.45 (s, 1H); 6.55 (d, 1H); 7.00 (t, 1H); 7.10 (d, 1H); 7.20-7.40 (m, 3H); 7.60 (d, 1H); 7.75 (d, 1H); 7.90 (s, 1H); 11.10 (s, 1H). MS m/z (%): 346 (MH+, 3%), 214 (31%), 199 (19%), 171 (14%).

Provenance & Evidence