反应详情

温度

92.5 °C

2-Bromoquinoline (3.19 g, 15.3 mmol, 1.0 eq), 3-methoxyphenyl boronic acid (2.79 g, 18.4 mmol, 1.2 eq) and K2CO3 (4.65 g, 33.7 mmol, 2.2 eq) were added to a dry 100 mL three-necked flask equipped with a magnetic stir bar and a condenser. Then the flask was evacuated and back-filled with nitrogen. The evacuation and back-fill procedure was repeated twice. Then solvent DME (38 mL), EtOH (12 mL) and H2O (17 mL) were added under nitrogen. The mixture was bubbled with nitrogen for 20 minutes and then Pd(PPh3)4 (0.53 g, 0.46 mmol, 0.03 eq) was added. The flask was then placed into an oil bath and heated to reflux (90-95° C.). The reaction was monitored by TLC, and about 19 hours later the starting material 2-bromoquinoline was consumed completely. Then the mixture was cooled to ambient temperature. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and then dried over sodium sulfate, and filtered and washed with ethyl acetate. The filtrate was concentrated and the residue was purified through column chromatography on silica gel using hexane and ethyl acetate (10:1) as an eluent to obtain the desired product 2-(3-methoxyphenyl)quinoline as a yellow liquid (3.76 g), which was used directly for the next step. A solution of the yellow liquid (3.75 g) in hydrogen bromide acid (25 mL, 48%) refluxed (110-120° C.) for 18 hours in an atmosphere of nitrogen. Then the mixture was cooled to ambient temperature and neutralized with a solution of K2CO3 in water until there was no gas to generate. Then the precipitate was filtered off and washed with water several times. The brown solid was dried in air under reduced pressure and product 3-(quinolin-2-yl)phenol 3.68 g was obtained. 1H NMR (DMSO-d6, 400 MHz): δ 6.74 (dd, J=8.0, 2.4 Hz, 1H), 7.18 (t, J=8.0 Hz, 1H), 7.43-7.48 (m, 3H), 7.65 (t, J=7.6 Hz, 1H), 7.86 (d, J=7.6 Hz, 1H), 7.92 (t, J=8.0 Hz, 2H), 8.37 (d, J=8.4 Hz, 1H), 9.52 (bs, 1H).

1. customequipped with a magnetic stir bar and a condenser
2. customThen the flask was evacuated
3. additionback-filled with nitrogen
4. additionThen solvent DME (38 mL), EtOH (12 mL) and H2O (17 mL) were added under nitrogen
5. customThe mixture was bubbled with nitrogen for 20 minutes
6. customThe flask was then placed into an oil bath
7. temperatureheated
8. customwas monitored by TLC, and about 19 hours
9. customwas consumed completely
10. temperatureThen the mixture was cooled to ambient temperature
11. customThe organic layer was separated
12. extractionthe aqueous layer was extracted with ethyl acetate
13. washThe combined organic layer was washed with water
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. washwashed with ethyl acetate
17. concentrationThe filtrate was concentrated
18. customthe residue was purified through column chromatography on silica gel