Tris(1,1-dimethylethyl)phosphine → 1-(Quinuclidin-3-yl)-1H-indol-5-amine

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Reaction Steps

Compound 69 (95 mg, 0.311 mmol), Tris(dibenzylideneacetone)dipalladium (0) (28.5 mg, 0.031 mmol) and anhydrous tetrahydrofuran (10 mL) were charged to a dry argon purged flask fitted with magnetic stir bar and condenser. A solution of tri-tert-butylphosphine (10 wt % in hexane, 125.9 mg, 0.062 mmol) is added followed by dropwise addition of a 1M tetrahydrofuran solution of Lithium bis(trimethylsilyl)amide (0.993 ml, 0.993 mmol) and mixture refluxed for a period of 45 minutes. The mixture was cooled to room temperature then to 0° C., quenched with 1M HCl (10 mL) and stirred for 15 minutes. The solution was diluted with ethyl acetate and conc. NH4OH added to adjust pH to 9. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95) to yield a yellow residue 70 (60 mg, 79.9%). 1H NMR (DMSO-d6) δ 1.22-1.47 (m, 2H), 1.57-1.70 (m, 1H), 1.73-1.90 (2×m, 2H), 2.66-2.84 (2×m, 3H), 2.97-3.04 (m, 1H), 3.09-3.20 (m, 2H), 4.41-4.54 (2×m, 3H), 6.17 (d, 1H, J=3.1 Hz), 6.51 (dd, 1H, J=8.8, 2.0 Hz), 6.68 (d, 1H, J=2.0 Hz), 7.12 (d, 1H, J=8.7 Hz), 7.50 (d, 1H, J=3.2 Hz); ESI-MS (m/z, %): 242 (MH+, 100%).

Provenance & Evidence