Sodium Carbonate → 7-(3-Phenyl-indole-1-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline Hydrochloride

関与物質

反応手順

3-Phenylindole [Heterocycl. Commun. (2000), 6(1), 59-62](2 mmol, 390 mg), was added to a stirred suspension of sodium hydride (40% oil dispersion, 88 mg, 2.2 mmol) in tetrahydrofuran (15 ml). When the effervescence ceased, 7-chlorosulfonyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid 2,2,2-trichloro-ethyl ester (D7) (840 mg, 2 mmol) was added and the mixture stirred at RT for 36 hours. The mixture was treated with saturated aq sodium carbonate (100 ml) and extracted with dichloromethane (3×50 ml). The combined extracts were dried (MgSO4) filtered and evaporated to afford a brown oil which was dissolved in THF (20 ml) and treated with sodium dihydrogen phosphate (10 ml) and zinc dust (1.0 g). The mixture was stirred vigorously for 36 h, filtered, washing the solid with water (10 ml) and THF (10 ml). The filtrate was treated with 10% aqueous potassium carbonate (20 ml) and the mixture extracted with dichloromethane (3×50 ml). The combined organic phase was dried (MgSO4), filtered, evaporated and the residue purified by flash chromatography (methanol-dichloromethane-aqueous ammonia) to afford the free base of the title compound δH (CHCl3)/ppm 2.73-2.79 (2H, m), 3.06 (2H, app.t), 3.94, 3.97 (2H, 2s), 7.03-7.69 (11H, m), 7.78 (1H, d), 8.04 (1H, d), MS[ES]: m/z (MH+) 389. This was converted to the title compound (E35) by treatment with 1M HCl in diethyl ether. Rf silica gel (1% (35% aq. NH3), 9% MeOH, 90% CHCl3) 0.40; δmax (CHCl3) 3422, 2959, 2761, 1604, 1445, 1372, 1166, 1134 cm-1; δH (CHCl3) 1.7 (2H, br.s), 3.09-3.10 (2H, m), 3.28-3.30 (2H, m), 4.24, 4.29 (2H, 2s), 7.19-7.78 (12H, m), 8.04 (1H, d); m.p. (diethyl ether-methanol) (with decomposition) 193-197° C.

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