Hydrochloric Acid → 1-(1,2,3,4-Tetrahydroisoquinolin-6-yl)ethan-1-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 6-trifluoromethanesulfonyloxy-3,4-dihydro-1H-isoquinoline-2-carboxylicacid tert-butyl ester (3.81 g, 10 mmol) in dry DMF (30 ml) are added n-butylvinyl ether (6.01 g, 60 mmol, 6.0 eq.), TEA (1.67 ml, 12 mmol, 1.2 eq.), 1,3-bis(diphenylphosphino)propane (144 mg, 0.276 mmol, 0.0276 eq.), and palladium acetate (56.1 mg, 0.25 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 80° C. for 7 hr. Water (100 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (30 ml×3). The combined organic layer is washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel flash chromatography (hexane/EtOAc 10:1) to give a mixture of the vinyl ether and the ketone product, which is dissolved in EtOAc (50 ml), and then treated with concentrated hydrochloric acid (3.0 ml). The mixture is stirred at rt for 2 hr, and then basified with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with EtOAc twice. The combined organic phase is dried with sodium sulfate and concentrated to give the title compound. MS (+VE) m/z 176.1 (M++1).

Provenance & Evidence