Trimethylsilylacetylene → HCID 90403368, compound

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of Example A4 (5.0 g, 18.8 mmol) in DMF (30 mL) was added TEA (7.87 mL, 56.5 mmol), Pd(PPh3)2Cl2 (0.661 g, 0.941 mmol), copper(I) iodide (0.179 g, 0.941 mmol), and trimethylsilylacetylene (7.9 mL, 56 mmol) and the mixture was stirred at 50° C. for 16 h. The mixture was diluted with EtOAc (60 mL) and filtered through diatomaceous earth, washing the pad with EtOAc (5×10 mL). The combined filtrates were concentrated to a volume of ˜20 mL, treated with a solution of TBAF (1M in THF, 38 mL, 38 mmol), and stirred at RT for 3 h. The mixture was partitioned between EtOAc (200 mL) and water (200 mL) and stirred for a few minutes. The resultant emulsion was filtered through diatomaceous earth, washing with water (2×20 mL) and EtOAc (3×20 mL). The filtrate layers were separated and the aqueous layer was extracted with EtOAc (50 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (EtOAc/Hex) to afford 3-((2-ethynylpyridin-4-yl)oxy)-2-methyl-6-nitropyridine (0.51 g, 10.6%) as a light brown solid. MS (ESI) m/z: 256.1 (M+H+).

Provenance & Evidence