反应详情

2-Bromo-1,3-thiazole (2.0 g, 13 mmol) and CuI (316 mg, 1.6 mmol) were combined in DME (25 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (5.8 mL, 42 mmol) and PdCl2(PPh3)2 (580 mg, 0.83 mmol) were added and 1-ethynyl-2-fluorobenzene (1.0 g, 8.3 mmol) was added dropwise. The reaction was heated under reflux for 4 h at which time GC/MS showed the reaction was complete. The mixture was filtered through Celite™, and the filter pad was washed thoroughly with ethyl acetate. The combined filtrates were concentrated in vacuo. The residue was dissolved in ethyl acetate (200 mL) and washed with water (200 mL), brine (200 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with hexane then 98:2 hexane:ethyl acetate to afford 2-[(2-fluorophenyl)ethynyl]-1,3-thiazole (700 mg, 41% yield) as a yellow oil that was impure by 1H NMR analysis. The compound (140 mg) was dissolved in DMSO and purified by preparative HPLC with a 30 min gradient from 50:50 water:acetonitrile to 100% acetonitrile to afford 2-[(2-fluorophenyl)ethynyl]-1,3-thiazole (53.2 mg, 75% yield) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.88 (d, J=3.0 Hz, 1H), 7.59–7.53 (m, 1H), 7.42–7.35 (m, 2H), 7.18–7.09 (m, 2H). MS (ESI) 204 (M++H).

1. customargon gas was bubbled through the suspension for several minutes
2. customto deoxygenate the mixture
3. temperatureThe reaction was heated
4. temperatureunder reflux for 4 h at which time GC/MS
5. filtrationThe mixture was filtered through Celite™
6. washthe filter pad was washed thoroughly with ethyl acetate
7. concentrationThe combined filtrates were concentrated in vacuo
8. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
9. washwashed with water (200 mL), brine (200 mL)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by column chromatography
14. washeluting with hexane