Triphenylphosphine → Ethyl 6-(4-hydroxy-2-methylphenyl)-2-quinolinecarboxylate

HRID 2423514Notes

Reaction equation

HRID 2423514 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=[CH:5]2.[OH:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[C:20]([CH3:27])[CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.O1CCOCC1>[OH:17][C:18]1[CH:23]=[CH:22][C:21]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=[CH:5]3)=[C:20]([CH3:27])[CH:19]=1

Participants

9

Reactant 4

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 27734484-Hydroxy-2-methylbenzeneboronic acidHCID 53404703Ethyl 6-bromoquinoline-2-carboxylate

Product 1

HCID 59321478Ethyl 6-(4-hydroxy-2-methylphenyl)-2-quinolinecarboxylateYield 60%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Palladium(II)acetate (3.2 mg, 14.5 μmol) was added to ethyl 6-bromo-2-quinolinecarboxylate (81.1 mg, 289.5 μmol), (4-hydroxy-2-methylphenyl)boronic acid (66.0 mg, 434.2 μmol), triphenylphosphine (7.6 mg, 29.0 μmol), and potassium phosphate (215.1 mg, 1.01 mmol). Then, dioxane (2.8 mL) was added to the mixture, followed by water (289.5 μL), and the reaction mixture was heated open to the atmosphere at 60° C. in an oil bath for 18 hours, then allowed to cool to room temperature. Water was added, followed by ethyl acetate, and the mixture was filtered through Celite®. The filtrate was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate, then filtered and concentrated. The residue was purified by silica gel chromatography eluting with 2:3 ethyl acetate:hexanes to give 53.2 mg (60%) of ethyl 6-(4-hydroxy-2-methylphenyl)-2-quinolinecarboxylate as a solid. 1H NMR (400 MHz, d6-DMSO): δ 9.51 (s, 1H), 8.56 (d, J=9 Hz, 1H), 8.16 (d, J=9 Hz, 1H), 8.13 (d, J=9 Hz, 1H), 7.98 (s, 1H), 7.82 (d, J=9 Hz, 1H), 7.16 (d, J=8 Hz, 1H), 6.74 (s, 1H), 6.71 (dd, J=8, 2 Hz, 1H), 4.43 (q, J=7 Hz, 2H), 2.23 (s, 3H), 1.39 (t, J=7 Hz, 3H). ESI-LCMS m/z 308 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. filtrationthe mixture was filtered through Celite®
  3. extractionThe filtrate was extracted with ethyl acetate
  4. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 2:3 ethyl acetate

Sources & evidence

ORD record
ord-31e096f942db4becb9af9f81a0d67a84
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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