4-Fluoroiodobenzene → 1-(4-fluorophenyl)-6-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinolin-2(1H)-one

HRID 1913893Notes

Reaction equation

HRID 1913893 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[NH:16][C:15](=[O:20])[CH2:14][CH2:13]3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:21][C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1.CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.[Cu](I)I>[F:21][C:22]1[CH:27]=[CH:26][C:25]([N:16]2[C:17]3[C:12](=[CH:11][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:19][CH:18]=3)[CH2:13][CH2:14][C:15]2=[O:20])=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 96054-FluoroiodobenzeneHCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 130542126-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 580650741-(4-fluorophenyl)-6-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinolin-2(1H)-oneYield 37.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
105 °C

Procedure

A suspension of 6-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinolin-2(1H)-one prepared in Example 10-(2) (0.20 g), 1-fluoro-4-iodobenzene (0.24 g), rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.10 g), copper iodide (0.035 g) and cesium carbonate (0.48 g) in toluene (1.0 mL) was stirred at 105° C. for 60 hours. The reaction mixture was cooled to room temperature, diluted with chloroform and filtered to remove insoluble materials. The filtrate was concentrated under reduced pressure. The resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: hexane/ethyl acetate=1/1), and the resulting solid was subjected to recrystallization from a mixture of diisopropyl ether and ethyl acetate to give the titled compound (0.10 g, 37%) as a colorless solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. customto remove insoluble materials
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: hexane/ethyl acetate=1/1)
  6. customthe resulting solid was subjected to recrystallization from a mixture of diisopropyl ether and ethyl acetate

Sources & evidence

ORD record
ord-e062adb7f33a4beca01abd29643fb987
Source dataset
uspto-grants-2013_12
Patent number
US08609847B2

Reaction notes

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