8-Hydroxyquinoline → methyl 4-(4-methyl-1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)pent-1-en-2-yl)benzoate

HRID 1520883Notes

Reaction equation

HRID 1520883 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 68156624methyl 4-(4-methyl-1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)pent-1-en-2-yl)benzoateYield 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-c5a1200e086848598b337d52c7e60105
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

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