Triethylamine → 4-Methyl-5-(phenylethynyl)-1,3-thiazole

Participants

Reaction Steps

5-Bromo-4-methyl-1,3-thiazole (570 mg, 3.2 mmol) and CuI (120 mg, 0.63 mmol) were combined in DME (5 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (2.0 mL, 14 mmol) and PdCl2(PPh3)2 (220 mg, 0.32 mmol) were added, followed by the dropwise addition of phenylacetylene (1.0 mL, 9.5 mmol). After 16 h stirring at ambient temperature additional phenylacetylene (0.35 mL, 3.2 mmol), CuI, (61 mg, 0.32 mmol), and PdCl2(PPh3)2 (110 mg, 0.16 mmol) were added and the reaction mixture was stirred for a further 16 h. The reaction was then heated to reflux, and after 3 h the reaction mixture was cooled, diluted with ethyl acetate (20 mL), and filtered through Celite™. The filter pad was washed thoroughly with ethyl acetate and the combined filtrates were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with 95:5 hexane:ethyl acetate to afford 4-methyl-5-(phenylethynyl)-1,3-thiazole (166 mg, 26% yield) as a red oil. 1H NMR (CDCl3, 300 MHz) δ 8.62 (s, 1H), 7.54–7.50 (m, 2H), 7.37–7.26 (m, 3H), 2.6 (s, 3H). MS (ESI) 200.1 (M++H).

Provenance & Evidence