[Synthesis]
General steps:
1. Under argon protection, Pd(OAc)? (13.5 mg, 0.06 mmol), PPh? (31.5 mg, 0.12 mmol), CuI (5.7 mg, 0.03 mmol) and 1-bromo-4-butylbenzene (639 mg, 3.00 mmol) were dissolved in triethylamine (1 mL). A solution of trimethylmethylsilylacetylene (324 mg, 3.30 mmol) was subsequently added.
2. The reaction mixture was stirred at 80 °C for 4 h. Upon completion of the reaction, it was acidified with 1N HCl aqueous solution.
3. Deionized water and EtOAc were added, partitioned and the organic layer was collected. The aqueous layer was extracted with EtOAc and the organic layers were combined.
4. The organic layer was washed with saturated brine, dried over anhydrous MgSO?, filtered and concentrated under reduced pressure.
5. The crude product was purified by silica gel column chromatography with the eluent of petroleum ether/EtOAc (100:1, v/v, Rf = 0.43) to afford 1-(4-butylphenyl)-2-trimethylsilylacetylene (S8) as a light yellow oil (550 mg, 2.40 mmol, 80% yield).
6. S8 (550 mg, 2.40 mmol) and K?CO? (495 mg, 3.58 mmol) were suspended in MeOH (12 mL) and stirred at room temperature for 4 hours.
7. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure.
8. Deionized water and EtOAc were added, partitioned and the organic layer was collected. The aqueous layer was extracted with EtOAc and the organic layers were combined.
9. The organic layer was washed with saturated brine, dried over anhydrous MgSO?, filtered and concentrated under reduced pressure.
10. The crude product was purified by silica gel column chromatography with the eluent petroleum ether/EtOAc (50:1, v/v, Rf = 0.50) to afford 1-butyl-4-ethynylbenzene (S9) as a light yellow oil (340 mg, 2.15 mmol, 90% yield).
11. Under argon protection, Pd(OAc)? (8.8 mg, 0.039 mmol), PPh? (20.5 mg, 0.078 mmol), CuI (3.7 mg, 0.020 mmol) and S9 (340 mg, 2.15 mmol) were dissolved in triethylamine (1 mL).
12. The reaction mixture was stirred at 80 °C for 4 h. Upon completion of the reaction, it was acidified with 1N HCl aqueous solution.
13. The reaction mixture was treated according to the post-synthesis treatment of S8, and the crude product was purified by silica gel column chromatography with the eluent of petroleum ether/EtOAc (50:1, v/v, Rf = 0.30) to afford 1-butyl-4-phenylethynyl (4c) as a yellow solid (340 mg, 1.17 mmol, 60% yield). |