A 30 mL reaction vial was flame dried and charged with isopropylamine (0.67 mL, 4.8 mmol) in toluene (3 mL). The solution was chilled to 0° C. before a 1.5M solution of nBuLi (4.8 mmol, 3.2 mL) was added. Pd2(dba)3 catalyst (184 mg, 0.2 mmol) was added, followed by ligand 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (160 mg, 0.4 mmol), and t-butylacetate (464 mg, 4 mmol). After 15 min, a toluene (3 mL) solution of 5-bromo-8-fluoroisoquinoline (200 mg, 0.9 mmol) was added. The reaction was stirred for 16 h while warming to 23° C. The crude mixture was purified by column chromatography (3% MeOH/DCM) to give tert-butyl 2-(8-fluoroisoquinolin-5-yl)acetate (140 mg). LCMS showed an m/z of 262.1 with a retention time of 1.469 min, method [1].
