Oxalyl chloride → 2-(6-chloro-1H-indol-3-yl)-2-oxoacetyl chloride

Participants

Reaction Steps

A solution of 6-chloro-1H-indole (15 g) in diethyl ether (300 mL) was cooled to 0° C. and treated with a solution of oxalyl chloride (9.4 mL) in diethyl ether (30 mL). The mixture was stirred for 16 hours at room temperature. Filtration gave 2-(6-chloro-1H-indol-3-yl)-2-oxoacetyl chloride as a crystalline material (15.5 g). A part of this product (2.5 g) was dissolved in dry tetrahydrofuran (25 mL) and added dropwise to a solution of 1-(1H-indol-4-yl)piperazine (1.4 g) and triethylamine (15 mL) in tetrahydrofuran (100 mL). After stirring for 16 hours the reaction mixture was concentrated in vacuo. The remaining oil was purified by flash chromatography (eluent: ethyl acetate/methanol/triethylamine 85:10:5) giving 1-(2-(6-chloro-1H-indol-3-yl)-1,2-dioxoethyl)-4-(1H-indol-4-yl)piperazine (1.6 g) as a crystalline material. This product was suspended in tetrahydrofuran (25 mL) and added dropwise to a suspension of lithium aluminium hydride (1.5 g) in tetrahydrofuran (50 mL). The mixture was refluxed for 4 hours and cooled to 0° C. followed by subsequent addition of water (3 mL), 15% aq. sodium hydroxide (1.5 mL), and water (7.5 mL). Filtration and standard work-up gave a yellow oil which was converted to the title oxalate salt (1.5 g) from an acetone solution by addition of oxalic acid. Mp 229-31° C. 1H NMR (DMSO-d6): 3.10 (t, 2H); 3.25-3.55 (m, 10H); 6.45 (s, 1H); 6.50 (d, 1H); 6.90-7.10 (m, 3H); 7.25-7.35 (m, 2H); 7.45 (s, 1H); 7.65 (d, 1H); 11.12 (s, 2H), MS m/z (%): 379 (MH+, 18%), 214 (16%), 199 (17%), 178 (16%), 143 (13%).

Provenance & Evidence