Sodium Iodide → Indole

Participants

Reaction Steps

To a solution of Intermediate 1 (0.20 g, 0.83 mmol) in anhydrous THF (100 ml), at 0° C., was added triethylamine (0.167 g, 1.65 mmol) and methane sulphonyl chloride (0.19 g, 1.65 mmol) and the mixture warmed to room temperature and stirred for 1.5 h. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (50 ml) and K2CO3 solution (10 ml). The aqueous was separated and extracted further with ethyl acetate (1×50 ml). The combined extracts were dried (MgSO4) and evaporated and used in the next step without further purification. To a solution of the preceding mesylate (0.264 g, 0.825 mmol), in isopropyl alcohol (25 ml), was added powdered K2CO3 (0.114 g, 0.825 mmol), sodium iodide (82 mg, 0.55 mmol) and (±)-1-H-4-(3-hydroxy-2-phenylpropyl)-piperazine (0.11 g, 0.55 mmol), and the mixture stirred at 120° C. for 16 h. The mixture was cooled to room temperature and the solvent removed in vacuo. The residue was partitioned between aq. K2CO3 solution (5 ml) and ethyl acetate (×3). The combined extracts were dried (MgSO4) and evaporated, and the residue chromatographed through silica gel eluting with CH2Cl2 /MeOH/NH3 (90:8:1) to give the title-indole (0.104 g, 43%). The 1.6 hydrogen oxalate salt was prepared. mp 137-140° C., (Found: C, 59.62: H, 6.67; N, 13.36. C26H32N6O. 1.6 (C2H2O4). 0.4 (C4H10O) requires C, 59.83; H, 6.39; N, 13.59%), m/e 445 (M+1)+, δ(360 MHz, D6 -DMSO) 1.92-2.06 (2H, m, CH2), 2.56-3.62 (17H, m, 8 of CH2 and CH), 7.18-7.34 (7H, m, Ar-H), 7.50 (1H, d, J=8.6 Hz, Ar-H), 7.79 (1H, s, Ar-H), 9.01 (2H, s, Ar-H), 11.17 (1H, s, NH).

Provenance & Evidence