Propyne → HCID 20616790, compound

Participants

Reaction Steps

DMF (50 mL) and NEt3 (10.30 mL, 73.9 mmol) were added to 2-bromo-4-fluorobenzaldehyde (10 g, 49.3 mmol) under argon in a 300 mL stainless steel reactor. The vessel was sparged with propyne and chilled in dry ice, then propyne (18.22 mL, 296 mmol) was distilled in. Bis(triphenylphosphine)palladium(II) chloride (0.173 g, 0.246 mmol) and copper(I) iodide (0.047 g, 0.246 mmol) were added, and the reactor was sealed and stirred for 4 hours at room temperature. The mixture was chilled and sampled. HPLC analysis indicated 90% conversion. 2 M NH3/MeOH (150 mL) was added to the chilled (and solidified) mixture, and the resulting solution was stirred 1.5 hours at 85° C. HPLC indicated complete conversion of alkyne to isoquinoline. The mixture was cooled and concentrated. Water (200 mL) and EtOAc (200 mL) were added, the layers were separated, and the organic layer was washed with brine (2×50 mL). The organic portion was extracted with 2N HCl (100 mL) and water (100 mL), then the aqueous layer was basified with 2N NaOH (120 mL). The mixture was extracted with EtOAc (2×100 mL) and the organic layer was washed with brine (50 mL), dried (Na2SO4), and concentrated, giving the title compound (6.87 g, 42.6 mmol, 87% yield). MS (DCI/NH3) m/z 162 (M+H)+.

Provenance & Evidence