1-Bromo-4-fluorobenzene → 1-Ethynyl-4-fluorobenzene

Temperature

50 °C

In a 1 Liter, round-bottom, three neck flask, a solution of 50 mL (0.51 Mol) ethynyltrimethylsilane, 1.5 g of palladium[II]acetate, 2.0 g of copper[I] iodide, 3.0 g of triphenylphosphine and 58 mL (0.52 Mol) of 4-bromofluorobenzene in 500 mL of de-aerated triethylamine were heated to 80° C. with stirring under an argon blanket for 2 hr. A white precipitate started to form after approximately 30 min. The reaction mixture was then cooled to 50° C. and stirred for an additional 2 h and then allowed to cool to room temperature with stirring overnight. The orange reaction mixture was filtered and a white precipitate of triethylamine hydrobromide was removed. The filtrate was concentrated by removal of the solvent. The residue was dissolved in 200 mL of dichloromethane and the resulting solution washed with water (3×150 mL), 5% HCl (3×150 mL), saturated sodium bicarbonate solution (3×150 mL), brine and then dried over sodium sulfate. After removal of the solvent, a clear oil was obtained 42.3 g (93%). The clear oil was further purified by dissolving the oil in 200 mL of methanol, to which 2 g of potassium carbonate was added with stirring. The stirring was continued overnight at ambient temperature. Upon distillation, 22.8 g, (0.19 Mol, 82%) of 1-ethynyl-4-fluorobenzene was obtained as a clear colorless liquid.

1. customto form after approximately 30 min
2. stirringstirred for an additional 2 h
3. temperatureto cool to room temperature
4. stirringwith stirring overnight
5. filtrationThe orange reaction mixture was filtered
6. customa white precipitate of triethylamine hydrobromide was removed
7. concentrationThe filtrate was concentrated by removal of the solvent
8. dissolutionThe residue was dissolved in 200 mL of dichloromethane
9. washthe resulting solution washed with water (3×150 mL), 5% HCl (3×150 mL), saturated sodium bicarbonate solution (3×150 mL), brine
10. dry with materialdried over sodium sulfate
11. customAfter removal of the solvent
12. customa clear oil was obtained 42.3 g (93%)
13. customThe clear oil was further purified
14. dissolutionby dissolving the oil in 200 mL of methanol
15. additionto which 2 g of potassium carbonate was added
16. stirringwith stirring
17. waitThe stirring was continued overnight at ambient temperature
18. distillationUpon distillation, 22.8 g

ORD record

ord-d1a63bde84e44a82a0d4a7f49f9c4548

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06303733B1