While under an atmosphere of argon, a flame-dried round-bottomed flask was charged with magnesium (1.5 g, 62.9 mmol) a small crystal of I2 and just enough dry THF to cover the magnesium. The mixture was heated to reflux until the color dissipated (about 10 min). Approximately 10% of a solution of 4-bromo-1-butene (61.7 mmol) in THF (100 mL) was added all at once. The remainder of the solution was added dropwise while maintaining a gentle reflux. After the addition was complete, heating was continued for 5 min (until almost all of the Mg had reacted). The newly formed Grignard reagent was then added to an ice cooled solution of tert-butyl 3-(3-(methoxy(methyl)amino)-3-oxopropyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (8.6 g, 24.7 mmol) in dry THF (100 mL). After stirring overnight at room temperature, the solution was poured into saturated aqueous ammonium chloride and extracted with ether (3×). The combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to give tert-butyl 3-(3-oxohept-6-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (8.0 g, 95%). ESI MS found for C21H29NO3 m/z [366.5 (M+23)]. The crude product was used without further purification.
