Phthalimide → (S)-2-(1-(2-chloro-7-fluoroquinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 75360Notes

Reaction equation

HRID 75360 reaction equation
[Cl:1][C:2]1[C:11]([C@H:12](O)[CH3:13])=[CH:10][C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][CH:8]=2)[N:3]=1.[C:16]1(=[O:26])[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:11]([C@@H:12]([N:20]2[C:16](=[O:26])[C:17]3[C:18](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:19]2=[O:21])[CH3:13])=[CH:10][C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][CH:8]=2)[N:3]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 42127712HCID 42127712, compound

Product 1

HCID 57707970(S)-2-(1-(2-chloro-7-fluoroquinolin-3-yl)ethyl)isoindoline-1,3-dioneYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (R)-1-(2-chloro-7-fluoroquinolin-3-yl)ethanol (3.03 g, 13.4 mmol), phthalimide (2.37 g, 1.20 eq) and PPh3 (4.23 g, 1.20 eq) in THF (70 mL) was added DIAD (3.13 mL, 1.20 eq) dropwise at 0° C. The mixture was then stirred at rt overnight before partitioning between EtOAc (200 mL) and water (200 mL). The organic layer was separated, washed with water, brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (DCM) to give a white foam of (S)-2-(1-(2-chloro-7-fluoroquinolin-3-yl)ethyl)isoindoline-1,3-dione (3.8 g, 80%). Mass Spectrum (ESI) m/e=355 (M+1).

Workup

  1. custombefore partitioning between EtOAc (200 mL) and water (200 mL)
  2. customThe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (DCM)

Sources & evidence

ORD record
ord-3a7dc362efff48f29751e51cc67c1fad
Source dataset
uspto-grants-2014_09
Patent number
US08835432B2

Reaction notes

Loading…