18-Crown-6 → (E)-2-(3-(3-(2,5-dimethylstyryl)phenyl)propyl)isoindoline-1,3-dione

HRID 628613Notes

Reaction equation

HRID 628613 reaction equation
[Br-].[CH3:2][C:3]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][C:4]=1[CH2:5][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1C.CC(C)([O-])C.[K+].C1OCCOCCOCCOCCOCCOC1.[O:55]=[C:56]1[C:64]2[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=2)[C:58](=[O:65])[N:57]1[CH2:66][CH2:67][CH2:68][C:69]1[CH:70]=[C:71]([CH:74]=[CH:75][CH:76]=1)[CH:72]=O>C1COCC1.C(Cl)Cl>[CH3:2][C:3]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][C:4]=1/[CH:5]=[CH:72]/[C:71]1[CH:70]=[C:69]([CH2:68][CH2:67][CH2:66][N:57]2[C:58](=[O:65])[C:59]3[C:64](=[CH:63][CH:62]=[CH:61][CH:60]=3)[C:56]2=[O:55])[CH:76]=[CH:75][CH:74]=1

Participants

7

Reactant 4

HCID 2855718-Crown-6HCID 23665647Potassium tert-butoxideHCID 577664653-(3-(1,3-Dioxoisoindolin-2-yl)propyl)benzaldehydeHCID 86632146HCID 86632146, compound

Product 1

HCID 68945031(E)-2-(3-(3-(2,5-dimethylstyryl)phenyl)propyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of the crude 2,5-dimethylmethylbenzyltriphenylphosphonium bromide in THF (10 mL) and CH2Cl2 (5 mL) were added potassium tert-butoxide (0.163 g, 1.45 mmol) and 18-crown-6 (0.163 g, 1.45 mmol). The mixture was stirred at room temperature under argon for 30 min then sonicated for 1 min. A solution of phthalimide 29 (0.193 g, 0.658 mmol) in CH2Cl2 (2 mL) was added and the mixture stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure and the residue partitioned between EtOAc and saturated aqueous NH4Cl. The combined organics were washed with brine, dried over MgSO4 and concentrated under reduced pressure. Purification by flash chromatography (20 to 50% EtOAc-hexanes) gave (E)-2-(3-(3-(2,5-dimethylstyryl)phenyl)propyl)isoindoline-1,3-dione as an oil. Yield (0.225 g, 86%), trans-/cis-isomer 1:1.5. Cis-isomer: 1H NMR (400 MHz, CDCl3) δ 7.69-7.76 (m, 4H), 6.91-7.44 (m, 7H) 6.63 (d, J=12.0 Hz, 1H), 6.57 (d, J=12.0 Hz, 1H), 3.81 (t, J=7.2 Hz, 2H), 2.75 (t, J=7.6 Hz, 2H), 2.44 (s, 3H), 2.39 (s, 3H), 2.08-2.17 (m, 2H).

Workup

  1. customthen sonicated for 1 min
  2. stirringthe mixture stirred at room temperature for 2 h
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customthe residue partitioned between EtOAc and saturated aqueous NH4Cl
  5. washThe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography (20 to 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-04c60d148f32427ba6f31fbd116328c9
Source dataset
uspto-grants-2016_04
Patent number
US09314467B2

Reaction notes

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