反应详情

温度

60 °C

To a solution of ethyl 4-iodobenzoate (5.0 g, 18.1 mmol) in DMF (15 mL) was added 3,4-difluorophenylacetylene (2.99 g, 21.7 mmol), Pd(Ph3P)4 (520 mg, 0.45 mmol), CuI (173 mg, 0.90 mmol) and diethylamine (3 mL). The reaction vessel was sealed and heated at 60° C. for 1 h in a microwave reactor. The reaction was cooled to room temperature, diluted with EtOAc:hexanes (2:1, 150 mL) and washed with water (2×100 mL) and brine (100 mL). The organic phase was dried over MgSO4, filtered and concentrated under vacuum. The crude product was dissolved in THF (60 mL) added MeOH (14 mL) and a solution of LiOH (1.52 g, 36.2 mmol) in water (14 mL). The reaction was stirred at room temperature and for 4 h. The reaction was acidified with 1 N HCl (60 mL) and 4-((3,4-difluorophenyl)ethynyl)benzoic acid was isolated (2.45 g, 57%) as a white solid; 1H-nmr (400 MHz, d6-DMSO) δ 7.96 (d, J=8.5 Hz, 2H), 7.73 (td, J=8.5, 2.0 Hz, 1H), 7.67 (d, J=8.5 Hz, 2H), 7.55-7.43 (m, 2H); LC (290 nM) 5.08 min (>98%); MS (ESI) m/z=258.7.

1. customThe reaction vessel was sealed
2. temperatureThe reaction was cooled to room temperature
3. washwashed with water (2×100 mL) and brine (100 mL)
4. dry with materialThe organic phase was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. dissolutionThe crude product was dissolved in THF (60 mL)
8. additionadded MeOH (14 mL)