8-Hydroxyquinoline → HCID 68156624, compound

HRID 537509Notes

Reaction equation

HRID 537509 reaction equation
[F:1][C:2]([F:9])([F:8])[C:3]1[CH:4]=[N:5][NH:6][CH:7]=1.N1C2C(=CC=CC=2O)C=CC=1.C(=O)([O-])[O-].[K+].[K+].Br[C:28]1[CH:33]=[CH:32][C:31]([CH:34]=[C:35]([C:40]2[CH:49]=[CH:48][C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=2)[CH2:36][CH:37]([CH3:39])[CH3:38])=[CH:30][CH:29]=1>CS(C)=O.[Cu]I>[CH3:38][CH:37]([CH3:39])[CH2:36][C:35]([C:40]1[CH:41]=[CH:42][C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:48][CH:49]=1)=[CH:34][C:31]1[CH:32]=[CH:33][C:28]([N:5]2[CH:4]=[C:3]([C:2]([F:9])([F:8])[F:1])[CH:7]=[N:6]2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 127777954-(Trifluoromethyl)-1H-pyrazoleHCID 68157244Methyl 4-(1-(4-bromophenyl)-4-methylpent-1-en-2-yl)benzoate

Product 1

HCID 68156624HCID 68156624, compoundYield 9.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

An oven-dried and nitrogen-cooled vial was charged with 4-trifluoromethyl pyrazole (77.0 mg, 0.56 mmol), quinolin-8-ol (10 mg, 0.07 mmol), copper(I) iodide (14 mg, 0.073 mmol), and potassium carbonate (140 mg, 1.0 mmol). A solution of methyl 4-(1-(4-bromophenyl)-4-methylpent-1-en-2-yl)benzoate (182.7 mg, 0.489 mmol) in dimethylsulfoxide (2.5 mL) was then added. The vial was capped and evacuated and back-filled with nitrogen four times. The reaction was then heated to 90° C. for 18 hours. The reaction was cooled to room temperature and partitioned between saturated ammonium chloride and ethyl acetate. The aqueous layer was extracted again with ethyl acetate, and the combined organics were dried over magnesium sulfate, filtered, and concentrated. Column chromatography (0-10% ethyl acetate in heptane) provided methyl 4-(4-methyl-1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)pent-1-en-2-yl)benzoate (19.8 mg, 9.5%) as an approximate 1:1 mixture of E/Z isomers. 1H NMR (400 MHz, CDCl3, δ): 8.20 (s, 1H), 8.06 (s, 1H), 8.05-8.01 (m, 2H), 7.98-7.93 (m, 2H), 7.91 (s, 1H), 7.83 (s, 1H), 7.71-7.66 (m, 2H), 7.53-7.49 (m, 2H), 7.46-7.42 (m, 2H), 7.41-7.36 (m, 2H), 7.24-7.20 (m, 2H), 7.01-6.96 (m, 2H), 6.78 (s, 1H), 6.49 (s, 1H), 3.92 (s, 3H), 3.90 (s, 3H), 2.62 (d, J=7.2 Hz, 2H), 2.41 (dd, J=7.2, 1.0 Hz, 2H), 1.70-1.48 (m, 2H), 0.90 (d, J=6.6 Hz, 6H), 0.80 (d, J=6.6 Hz, 6H). MS (M+1): 429.3.

Workup

  1. customAn oven-dried
  2. temperaturenitrogen-cooled vial
  3. customThe vial was capped
  4. customevacuated
  5. additionback-filled with nitrogen four times
  6. temperatureThe reaction was cooled to room temperature
  7. custompartitioned between saturated ammonium chloride and ethyl acetate
  8. extractionThe aqueous layer was extracted again with ethyl acetate
  9. dry with materialthe combined organics were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-aaf9ec970bcf42aa9d04b56eb9d3ada9
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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