Phthalimide → 2-[(3-Bromo-6-quinolinyl)methyl]-1H-isoindole-1,3(2H)-dione

HRID 1892418Notes

Reaction equation

HRID 1892418 reaction equation
[C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Br:45][C:46]1[CH:47]=[N:48][C:49]2[C:54]([CH:55]=1)=[CH:53][C:52]([CH2:56]O)=[CH:51][CH:50]=2>C1COCC1.CCOC(C)=O>[Br:45][C:46]1[CH:47]=[N:48][C:49]2[C:54]([CH:55]=1)=[CH:53][C:52]([CH2:56][N:5]1[C:1](=[O:11])[C:2]3[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:4]1=[O:6])=[CH:51][CH:50]=2

Participants

7

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 58190515HCID 58190515, compound

Product 1

HCID 581905432-[(3-Bromo-6-quinolinyl)methyl]-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of phthalimide (281 mg, 1.9 mmol), triphenyl phosphine (500 mg, 1.9 mmol) in 10 mL of THF was added DIAD (386 mg, 1.9 mmol) dropwise at 0° C. and the mixture was stirred at this temperature for 10 min. (3-Bromo-quinolin-6-yl)-methanol (413 mg, 1.7 mmol) was added to the above solution in one portion and the resulting solution was stirred at rt for 30 min, then heated at 40° C. for 5 h. After cooling, the reaction mixture was taken up with EtOAc, washed with water, extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with EtOAc/hexane gradient to afford the title compound. 1H-NMR (400 MHz, CDCl3) δ ppm 8.89 (d, 1H), 8.31 (d, 1H), 8.06 (d, 1H), 7.90-7.86 (m, 3H), 7.82-7.73 (m, 3H), 5.04 (s, 2H). LCMS (method A): [MH]+=368/370, tR=5.54 min.

Workup

  1. additionwas added to the above solution in one portion
  2. temperatureheated at 40° C. for 5 h
  3. temperatureAfter cooling
  4. washwashed with water
  5. extractionextracted with EtOAc
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel eluting with EtOAc/hexane gradient

Sources & evidence

ORD record
ord-95d5098570ff4ce5a88d1e39a64b994c
Source dataset
uspto-grants-2013_08
Patent number
US08507676B2

Reaction notes

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