2-Ethynyl-4-Methylthiazole

1365214-91-0

211940-25-9

1. 2b (2.00 g, 8.89 mmol), trimethylsilylacetylene (1.30 mL, 9.20 mmol), PdCl2(PPh3)2 (65 mg, 0.093 mmol) and CuI (45 mg, 0.24 mmol) were dissolved in anhydrous triethylamine (15 mL) under nitrogen protection. 2. The reaction mixture was heated to reflux temperature with continuous stirring for 18 hours. 3. trimethylsilylacetylene (0.62 mL, 4.4 mmol) was added to the reaction mixture and stirring was continued at reflux temperature for 1 hour. 4. Upon completion of the reaction, the solvent was removed by evaporation under reduced pressure and the residue was diluted with chloroform and washed with saturated aqueous sodium bicarbonate. 5. The organic layer was separated, dried with anhydrous sodium sulfate, filtered and concentrated to obtain the crude product. 6. The crude product was purified by silica gel column chromatography using 0-20% ethyl acetate/hexane gradient elution to afford 4-methyl-2-[(trimethylsilyl)ethynyl]-1,3-thiazole (1.08 g, 62%). 7. 4-Methyl-2-[(trimethylsilyl)ethynyl]-1,3-thiazole (10.0 g, 51.2 mmol) was dissolved in methanol (100 mL) and potassium carbonate (8.50 g, 61.5 mmol) was added. 8. The reaction mixture was stirred at room temperature for 15 minutes, then filtered to remove insoluble material and the filtrate was concentrated under reduced pressure. 9. Water was added to the residue and extracted with ethyl acetate. 10. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered and concentrated. 11. The crude product was purified by silica gel column chromatography using a 10-20% ethyl acetate/hexane gradient elution to afford 2-alkynyl-4-methylthiazole (5.58 g, 88%).