[C:1]([C:4]1[N:9]=[C:8]([Cl:10])[C:7]([OH:11])=[C:6](I)[CH:5]=1)(=[O:3])[CH3:2].[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15].C(N(CC)CC)C>C(Cl)(Cl)Cl.O1CCCC1.C(OCC)(=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([C:4]1[N:9]=[C:8]([Cl:10])[C:7]([OH:11])=[C:6]([C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13])[CH:5]=1)(=[O:3])[CH3:2]
6-Acetyl-2-chloro-3-hydroxy-4-iodo-pyridine (6.12 g, 20.6 mmole) was combined with trimethylsilyl acetylene (3.5 ml, 24.7 mmole), bis (triphenylphosphine) palladium dichloride (730 mg, 10 mmole) and cuprous iodide (99 mg, 0.52 mmole) in 37 ml of 2:1 chloroform/tetrahydrofuran in a 100 ml one neck round bottom flask under nitrogen. The suspension was treated with triethylamine (6 ml, 43 mmole) and the reaction was stirred for 2 h at room temperature. The mixture was diluted with 150 ml of ethyl acetate and was washed with 2×50 ml of 5% hydrochloric acid. The organics were dried over anhydrous magnesium sulfate, treated with 10 g of silica gel (230-400 mesh), and concentrated to dryness. The plug was chromatographed over 200 g of silica gel (230-400 mesh), eluting with 25% ethyl acetate/hexane+0.1% acetic acid, while collecting 50 ml fractions. Fractions 10-18 were combined and concentrated to give 4.88 g (88%) of 6-acetyl-2-chloro-3-hydroxy-4-(2-trimethylsilylethynyl)pyridine as a pale tan solid. 1H NMR (d6DMSO): δ 8 0.26 (s, 9), 2.51 (s, 3), 7.78 (s, 1) ppm.
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