Phthalimide → 2-(1-(5-Chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 2044964Notes

Reaction equation

HRID 2044964 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH:19](O)[CH3:20])[C:6]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)=[N:7]2.O1CCCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:46]1(=[O:56])[NH:50][C:49](=[O:51])[C:48]2=[CH:52][CH:53]=[CH:54][CH:55]=[C:47]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O>>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH:19]([N:50]1[C:46](=[O:56])[C:47]3[C:48](=[CH:52][CH:53]=[CH:54][CH:55]=3)[C:49]1=[O:51])[CH3:20])[C:6]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)=[N:7]2

Participants

6

Reactant 5

HCID 6809PhthalimideHCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 577080321-(5-Chloro-2-(3-fluorophenyl)quinolin-3-yl)ethanol

Product 1

HCID 577079992-(1-(5-Chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

Procedure

To a solution of 1-(5-chloro-2-(3-fluorophenyl)quinolin-3-yl)ethanol (0.9927 g, 3.290 mmol) in tetrahydrofuran (32.90 mL, 3.290 mmol) were added triphenylphosphine (2.589 g, 9.870 mmol), phthalimide (1.452 g, 9.870 mmol), and diisopropyl azodicarboxylate (1.943 mL, 9.870 mmol). The reaction mixture was stirred at room temperature. After 1.5 h, the mixture was concentrated under reduced pressure and partitioned between EtOAc (100 mL) and brine (100 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and 50% isocratic of EtOAc for 10 min as eluent to give 2-(1-(5-chloro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione as a light yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.84 (1 H, s), 7.98-8.04 (1 H, m), 7.85-7.90 (1 H, m), 7.82 (1 H, s), 7.74-7.81 (2 H, m), 7.65-7.71 (2 H, m), 7.21-7.33 (2 H, m), 7.12-7.19 (2 H, m), 5.76-5.82 (1 H, m), 1.83 (3 H, d, J=6.7 Hz); LC-MS (ESI) m/z 431.0 [M+H]+.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. custompartitioned between EtOAc (100 mL) and brine (100 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  7. customover 25 min

Sources & evidence

ORD record
ord-c3449caa776f4626aeedd4ea7a2f6136
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

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