Tetrahydrofuran → 4-(2-Phenylethynyl)benzoic acid

Temperatur

10 °C

The 4-iodo-benzoic acid methyl ester 1 (20.0 g, 76.34 mmol), ethynyl-benzene 2 (8.56 g, 83.96 mmol), PdCl2(PPh3)2 (0.65 g, 0.92 mmol), and CuI (0.35 g, 1.83 mmol) were mixed with THF (110 ml) in a round bottom under argon. The dry THF was sparged with dry, oxygen-free argon for at least 5 min. immediately before use. The reaction was cooled to 10° C. and TEA (16 ml) was added. The cooling bath was removed and the reaction was stirred at RT under argon. After 2.5 h, the reaction was diluted with EtOAc (400 ml) and the solids were filtered off through a pad of celite. The organic filtrate was washed with 1M HCl (60 ml), sat. aq. NaHCO3 (60 ml), water (60 ml), brine (60 ml), dried with Na2SO4, filtered and concentrated under reduced pressure. The crude solid methyl ester was dissolved in MeOH (400 ml), 6M NaOH (30 ml) and water (50 ml). The reaction was stirred at 70° C. until a clear solution was formed (about 1 h). The reaction could be followed by LCMS. The reaction was cooled and diluted with water (500 ml) and hexane (100 ml). The pH was adjusted to pH 6-7. The white solid that formed was collected and washed with water (3×60 ml) and hexane (3×60 ml). The solid 3 was dried in vacuo yielding 17.3 g (approximately quantitative yield in 99% purity).

1. customThe dry THF was sparged
2. customwith dry
3. waitoxygen-free argon for at least 5 min. immediately before use
4. additionTEA (16 ml) was added
5. customThe cooling bath was removed
6. additionthe reaction was diluted with EtOAc (400 ml)
7. filtrationthe solids were filtered off through a pad of celite
8. washThe organic filtrate was washed with 1M HCl (60 ml), sat. aq. NaHCO3 (60 ml), water (60 ml), brine (60 ml)
9. dry with materialdried with Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. dissolutionThe crude solid methyl ester was dissolved in MeOH (400 ml)
13. stirringThe reaction was stirred at 70° C. until a clear solution
14. customwas formed (about 1 h)
15. customThe reaction
16. temperatureThe reaction was cooled
17. customThe white solid that formed
18. customwas collected
19. washwashed with water (3×60 ml) and hexane (3×60 ml)
20. dry with materialThe solid 3 was dried in vacuo
21. customyielding 17.3 g (approximately quantitative yield in 99% purity)

ORD-Eintrag

ord-63aef9ea3c484c6bb354f6dcd4aa43f3

Quelldatensatz

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08153843B2