Phthalimide → 2-(1-(2,5-Dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 216802Notes

Reaction equation

HRID 216802 reaction equation
[Cl:1][C:2]1[C:11]([CH:12](O)[CH3:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[Cl:15])[N:3]=1.S(Cl)(Cl)=O.ClC1C(C(Cl)C)=CC2C(=CC=CC=2Cl)N=1.[C:35]1(=[O:45])[NH:39][C:38](=[O:40])[C:37]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:36]12.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[Cl:1][C:2]1[C:11]([CH:12]([N:39]2[C:35](=[O:45])[C:36]3[C:37](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:38]2=[O:40])[CH3:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[Cl:15])[N:3]=1

Participants

8

Reactant 5

HCID 6809PhthalimideHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 577079561-(2,5-Dichloroquinolin-3-yl)ethanolHCID 577080552,5-Dichloro-3-(1-chloroethyl)quinoline

Product 1

HCID 577078732-(1-(2,5-Dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
55 °C

Procedure

Added DCM (2 mL) to 1-(2,5-dichloroquinolin-3-yl)ethanol (200 mg, 826 μmol). Added thionyl chloride (301 μl, 4131 μmol). Obtained a clear colorless solution within minutes. Concentrated reaction mixture to dryness on the rotavap to obtain an oil, which was used without further purification. LC-MS (+esi, M+H+=260.0). Dissolved 2,5-dichloro-3-(1-chloroethyl)quinoline (215 mg, 825 μmol) in DMF (2 mL) and added phthalimide (127 mg, 866 μmol) and K2CO3 (228 mg, 1650 μmol). Submerged in oil bath and began heating to 55° C. After 10 min the temperature of the oil bath was raised to 80° C. After 30 more minutes the reaction mixture was partitioned between EtOAc:H2O. The organic layer was washed with water (3×), dried with sodium sulfate, filtered, and concentrated. The crude was solid was chromatographed on 12 g silica gel column with 0-20% EtOAc:Hex. The desired fractions were combined and concentrated to yield a white crystalline solid. 1H NMR (400 MHz, DICHLOROMETHANE-d2) δ ppm 1.99 (d, J=7.04 Hz, 3H) 5.93 (q, J=7.17 Hz, 1H) 7.64-7.70 (m, 2H) 7.71-7.76 (m, 2H) 7.77-7.83 (m, 2H) 7.88-7.93 (m, 1H) 8.95 (s, 1H). LC-MS (+esi, M+H+=371.0)

Workup

  1. customObtained a clear colorless solution within minutes
  2. concentrationConcentrated
  3. customreaction mixture to dryness on the rotavap
  4. customto obtain an oil, which
  5. customwas used without further purification
  6. customSubmerged in oil bath
  7. temperatureAfter 10 min the temperature of the oil bath was raised to 80° C
  8. customAfter 30 more minutes the reaction mixture was partitioned between EtOAc
  9. washThe organic layer was washed with water (3×)
  10. dry with materialdried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customwas chromatographed on 12 g silica gel column with 0-20% EtOAc
  14. concentrationconcentrated
  15. customto yield a white crystalline solid

Sources & evidence

ORD record
ord-697e113ca1e3491183e7911f50628c3d
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

Loading…