Phenylacetylene → 1(2H)-Pyridinebutanoic acid, 5-fluoro-α-methyl-α-(methylsulfonyl)-2-oxo-4-(2-phenylethynyl)-, ethyl ester, (αR)-

Participants

Reaction Steps

A solution of ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (500 mg, 1.12 mmol) and diisopropylethylamine (6.0 mL, 30 mmol) in tetrahydrofuran (15 mL) was degassed with nitrogen. Pd(PPh3)4 (65.4 mg, 0.056) and copper iodide (21.8 mg, 0.112 mmol) were added to the solution, followed by phenylacetylene (150 uL, 1.4 mmol). The reaction was allowed to stir until complete via TLC. The reaction was diluted with EtOAc (100 mL) and washed with saturated aq NH4Cl (100 mL) and brine (100 mL), dried (MgSO4), filtered, and concentrated. The crude residue was purified via flash chromatography using a Varian SF15-24 g column and an eluent of EtOAc in hexanes (30-80%) to afford the title compound as a yellow solid (389 mg, 82.6%). MS (LCMS) m/z 420.0 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) ppm 1.35 (t, 3 H) 1.75 (s, 3 H) 2.42-2.61 (m, 2 H) 3.11 (s, 3 H) 3.91-4.00 (m, 1 H) 4.19-4.27 (m, 1 H) 4.30 (q, J=7.02 Hz, 2 H) 6.72 (d, J=6.63 Hz, 1 H) 7.27 (t, J=2.34 Hz, 2 H) 7.35-7.44 (m, 2 H) 7.55-7.60 (m, 2 H).

Provenance & Evidence