Reaktion #1596819

Reaktionsgleichung

2-bromoquinoline

2-Bromoquinoline

3-methoxyphenyl boronic acid

K2CO3

→

desired product

3-(quinolin-2-yl)phenol

2-(3-methoxyphenyl)quinoline

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeequipped with a magnetic stir bar and a condenser
2. 2
   SonstigeThen the flask was evacuated
3. 3
   workup.ADDITIONback-filled with nitrogen
4. 4
   workup.ADDITIONThen solvent DME (38 mL), EtOH (12 mL) and H2O (17 mL) were added under nitrogen
5. 5
   SonstigeThe mixture was bubbled with nitrogen for 20 minutes
6. 6
   SonstigeThe flask was then placed into an oil bath
7. 7
   Temperaturheated
8. 8
   Sonstigewas monitored by TLC, and about 19 hours
9. 9
   Sonstigewas consumed completely
10. 10
    TemperaturThen the mixture was cooled to ambient temperature
11. 11
    SonstigeThe organic layer was separated
12. 12
    Extraktionthe aqueous layer was extracted with ethyl acetate
13. 13
    WaschenThe combined organic layer was washed with water
14. 14
    Trocknendried over sodium sulfate
15. 15
    Filtrationfiltered
16. 16
    Waschenwashed with ethyl acetate
17. 17
    EinengenThe filtrate was concentrated
18. 18
    Sonstigethe residue was purified through column chromatography on silica gel

Vorschrift

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).

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