Potassium Carbonate → 2-(3-Methoxyphenyl)quinoline

HRID 1509637Notes

Reaction equation

HRID 1509637 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[CH:11][C:2]=1[C:18]1[CH:19]=[C:14]([OH:13])[CH:15]=[CH:16][CH:17]=1.[CH3:12][O:13][C:14]1[CH:19]=[C:18]([C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 27627562-Bromoquinoline2×

Product 2

HCID 14819923-(2-Quinolinyl)benzenolHCID 125036682-(3-Methoxyphenyl)quinolineYield 208.9%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
92.5 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-18c04678c5d440eb921abaa42844bdcd
Source dataset
uspto-grants-2015_12
Patent number
US09224963B2

Reaction notes

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