Potassium Carbonate → 1-(6-(4-Acetylphenyl)quinolin-2-yl)ethanone

HRID 625642Notes

Reaction equation

HRID 625642 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].Br[C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([C:24](=[O:26])[CH3:25])[CH:18]=[CH:17]2.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[N:20]=[C:19]([C:24](=[O:26])[CH3:25])[CH:18]=[CH:17]3)=[CH:6][CH:5]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 37021224-Acetylphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574581651-(6-Bromoquinolin-2-yl)ethanone

Product 1

HCID 584988521-(6-(4-Acetylphenyl)quinolin-2-yl)ethanoneYield 96.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Pd(OAc)2 (62.9 mg, 0.280 mmol) was added to a solution of 4-acetylphenylboronic acid (689 mg, 4.20 mmol), 1-(6-bromoquinolin-2-yl)ethanone (700 mg, 2.8 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (230 mg, 0.560 mmol) and K2CO3 (1.16 g, 8.40 mmol) in dioxane (10 mL) and water (2.500 mL) and the reaction mixture was refluxed at 110° C. for 5 h. The reaction mixture was cooled to rt and partitioned between sat.aq NH4Cl and EtOAc. The organic layer was washed with NaHCO3 and brine and then dried (MgSO4), filtered, concentrated and purified by flash silica gel chromatography (loading solvent: DCM, eluted with 0˜20% EtOAc/hexanes) to yield 1-(6-(4-acetylphenyl)quinolin-2-yl)ethanone (781 mg) as white solid. LC-MS retention time 3.776 min; m/z 290.29 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, chloroform-d) δ ppm 8.35 (d, J=8.3 Hz, 1H), 8.34 (d, J=8.3 Hz, 1H), 8.19 (d, J=8.5 Hz, 1H), 8.12 (d, J=8.3 Hz, 1H), 8.08-8.16 (m, 3H), 7.85 (d, J=8.3 Hz, 1H), 7.82-7.89 (m, 1H), 2.91 (s, 3H), 2.69 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. custompartitioned between sat.aq NH4Cl and EtOAc
  3. washThe organic layer was washed with NaHCO3 and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash silica gel chromatography (loading solvent: DCM, eluted with 0˜20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-eabc4cc6d77a4c979f91dd70c931689e
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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